Curr. Pharm. Des. [JOURNAL]
Sun
200 papers
Machine Learning-Enabled Exploration of Bryophyllum Pinnatum Phytoconstituents for Urolithiasis Management: Molecular Docking, MMGBSA Analysis, ADMET Profiling, MD simulations, and Toxicity Assessment.
Haque Z, Taleuzzaman M, Alhazmi HA … +6 more , Alam MS, Mohd Siddique MU, Zoghebi K, Jamal R, Mawkili W, Makeen HA
Curr Pharm Des · 2026 May · PMID 42152638 · Publisher ↗
INTRODUCTION: The development of stones in the urinary tract, particularly in the kidneys, is a common symptom of urolithiasis, commonly referred to as kidney stone disease. The risk of stone formation persists due to li...
INTRODUCTION: The development of stones in the urinary tract, particularly in the kidneys, is a common symptom of urolithiasis, commonly referred to as kidney stone disease. The risk of stone formation persists due to lifestyle, metabolic, and genetic factors, and recurrence is high even with advancements in surgical and pharmaceutical treatments. MATERIAL AND METHODS: To treat urolithiasis, this study used an in-silico approach backed by machine learning to examine the therapeutic potential of naturally occurring compounds identified in Bryophyllum pinnatum. Molecular docking, molecular dynamics (MD) simulations, MM-GBSA binding energy analysis, and toxicity profiling were the primary techniques employed. Carbonic anhydrase, urease, calcium-sensing receptor (CaSR), and prostaglandin receptor are vital proteins contributing to kidney stone development. The study aimed to determine the binding and inhibitory potential of the selected phytochemicals against these targets. RESULTS: The tested compounds showed considerable binding affinities, with BP1, BP3, BP8, BP10, and BP25 exhibiting potentially significant interactions with the target proteins. Interestingly, compound BP3 had a docking score of -9.2 kcal/mol against carbonic anhydrase, forming hydrophobic contacts and stable hydrogen bonds necessary for potent inhibition. Molecular dynamics simulations of 200 nanoseconds revealed low RMSD and RMSF values, similar to standard reference compounds, indicating that the ligand-protein complexes remained stable throughout the simulation. DISCUSSION: BP3 and BP8 were placed in toxicity class 5 based on toxicity evaluations using ADMET predictions and ProTox-II, suggesting low toxicity and a favorable safety profile for potential therapeutic use. The computational results indicate that phytoconstituents from Bryophyllum pinnatum are promising candidates for developing safer and more effective plant-based kidney stone treatments. CONCLUSION: This study opens the door to targeted phytotherapeutic approaches that may improve urolithiasis treatment strategies.
Molecular Modeling and Systems Pharmacology Approaches to Polyphenols in Urolithiasis Therapy.
Srivastava AK, Kumar A, Ashesh AM … +2 more , Radheshyam, Kumar P
Curr Pharm Des · 2026 May · PMID 42152637 · Publisher ↗
Urolithiasis, a condition characterized by the formation of stones in the urinary tract, remains prevalent and frequently recurring. Its development is driven by multiple factors, including oxidative stress, inflammation...
Urolithiasis, a condition characterized by the formation of stones in the urinary tract, remains prevalent and frequently recurring. Its development is driven by multiple factors, including oxidative stress, inflammation, crystal aggregation, and injury to renal epithelial cells. Current treatment options often provide only short-term relief and fail to effectively prevent recurrence or target the complex biological pathways involved. In this context, natural polyphenols-bioactive compounds found abundantly in plant-based foods and traditional medicinal herbs-have gained attention for their potential therapeutic effects, including antioxidant, anti-inflammatory, and crystal nucleation inhibition, as well as kidney-protective actions. However, their precise molecular mechanisms and biological targets are still not fully understood, largely due to their interactions with diverse cellular pathways. Systems pharmacology and molecular modeling offer promising tools for exploring the antiurolithiatic potential of polyphenolic compounds. Systems pharmacology allows researchers to map polyphenol interactions across various biological networks, linking them to key mechanisms implicated in stone formation, such as oxidative balance via Nrf2/HO-1, inflammation through NF-κB and TNF-α signaling, and regulation of crystallization by proteins like osteopontin and uromodulin. Complementary to this, molecular modeling approaches such as molecular docking, dynamics simulations, and structure-activity relationship (SAR) studies enable visualization and analysis of the binding affinities between polyphenols and urolithiasis-related targets at the atomic level. Together, these computational approaches provide a powerful platform for the rational design and optimization of polyphenol-based therapeutics. This integrative strategy not only deepens our understanding of how these compounds work but also supports the development of multitarget plant-derived drugs for the prevention and management of kidney stones. Moving forward, combining these techniques with experimental validation and incorporating artificial intelligence could greatly enhance the efficiency and accuracy of natural product drug discovery.
Cell-free DNA Methylation Analysis, a Noninvasive Biomarker for Detection, Prediction, Classification, and Treatment Monitoring for Brain Tumors.
Hooshyari Ardakani R, Rahimi H, Mohamadi-Zarch SM … +1 more , Bagheri SM
Curr Pharm Des · 2026 May · PMID 42152636 · Publisher ↗
BACKGROUND AND OBJECTIVE: Brain tumors represent a major clinical challenge due to difficulties in early detection and precise molecular characterization. Recent advances in liquid biopsy have highlighted cellfree DNA (c...
BACKGROUND AND OBJECTIVE: Brain tumors represent a major clinical challenge due to difficulties in early detection and precise molecular characterization. Recent advances in liquid biopsy have highlighted cellfree DNA (cfDNA) methylation profiling as a promising non-invasive approach for the detection, classification, prognostication, and longitudinal monitoring of brain tumors. METHODS: A literature search was performed using the PubMed database covering studies published up to July 2025. The search terms "cell-free DNA methylation" and "brain tumors" were applied. Eligible studies investigated cfDNA methylation for early diagnosis, molecular classification, prognostic assessment, or treatment monitoring, with a particular focus on gliomas and medulloblastomas. Key findings were qualitatively summarized. RESULTS: cfDNA methylation profiling consistently demonstrated high diagnostic accuracy, with reported sensitivities and specificities frequently exceeding 97%. This approach enables early tumor identification, detection of brain metastases, and accurate classification of central nervous system tumors in both adult and pediatric cohorts. Furthermore, cfDNA methylation dynamics provide valuable insights into treatment response and the emergence of therapeutic resistance, including resistance to CDK4/6 inhibitors. Cerebrospinal fluid generally outperforms plasma in sensitivity due to its closer proximity to the tumor microenvironment. Advanced methodologies such as cfMeDIP-seq, enzymatic methylation sequencing, and nanopore sequencing have further improved performance with low-input cfDNA. CONCLUSION: cfDNA methylation analysis is a highly sensitive and minimally invasive tool with substantial potential to improve early diagnosis, molecular stratification, and real-time monitoring of brain tumors. Despite existing technical and pre-analytical challenges, large-scale prospective studies are warranted to enable clinical translation and standardization.
Dual Disruption: Targeting Mitotic Processes and Epigenetic Regulation to Overcome Anticancer Drug Resistance.
Bhardwaj K, Jain A, Goel K … +3 more , Kaur R, Singh TG, Mujwar S
Curr Pharm Des · 2026 May · PMID 42152635 · Publisher ↗
Drug resistance is a considerable challenge to the existing cancer therapy resulting in disease reappearance and progression despite initial treatment success. The disruption of mitotic and epigenetic regulatory networks...
Drug resistance is a considerable challenge to the existing cancer therapy resulting in disease reappearance and progression despite initial treatment success. The disruption of mitotic and epigenetic regulatory networks represents an innovative approach for cancer therapy. Mitotic regulators, including Aurora kinases (AURKA), Polo-like kinases (PLKs), and kinesins, are essential for chromosomal segregation for the development of newer progeny cells during the cell cycle process. However, it is a highly complex process and its dysregulation results in aneuploidy and intratumoral heterogeneity responsible for cancerous growth. Parallelly, epigenomic alterations by dysfunctional histone deacetylases (HDAC), DNA methyltransferases, and bromodomain and extra-terminal (BET) proteins result in modified chromatin architecture. Responsible for stemness, immunological evasion, and phenotypic plasticity. The association of these two processes of cell division results in the survival of cancerous cells. Epigenetic flexibility results in bypassing mitotic checkpoint failures by cancerous cells to modify epigenetic programming responsible for the evasion of therapeutic interventions. Combination therapies that target both pathways demonstrate enhanced cytotoxicity, extend the time before resistance manifests, and effectively eliminate drug-tolerant cancerous cells in aggressive cancers such as triple-negative breast cancer, glioblastoma, and hematological malignancies. This review highlights the therapeutic innovation offered by dual disruption, where the combination of targeting mitotic fidelity and epigenetic plasticity creates a vulnerability that is not possible through separate treatments. The combination of inducing mitotic stress and at the same time preventing chromatin-based adaptive rewiring, this strategy limits the formation of drug-tolerant persistent.
Multifaceted Modulation of Tumor Microenvironment Dynamics: Emerging Cross-Disciplinary Paradigms in Precision Drug Delivery.
Soni S, Rathee S, Patil UK
Curr Pharm Des · 2026 May · PMID 42152634 · Publisher ↗
Cancer is one of the leading global public health challenges, thus creating a pressing need to develop novel therapies that combine concepts from various scientific disciplines. In this review, we have evaluated how adva...
Cancer is one of the leading global public health challenges, thus creating a pressing need to develop novel therapies that combine concepts from various scientific disciplines. In this review, we have evaluated how advancements in artificial intelligence, cancer research, and materials science have collectively influenced modern cancer therapies. Cancer research, in particular, is focusing on the tumor microenvironment (TME), which is a highly complex, dynamic, and heterogeneous environment consisting of cancer cells, stromal components, immune cells, and paracrine factors that collectively orchestrate cancer development, progression, metastasis, and drug resistance. Modern analytical tools, including artificial intelligence, have been developed to integrate various omics data, medical images, and clinical information to understand TME, detect potential drug targets, and accurately predict drug response in cancer therapy. Simultaneously, advancements in materials science have led to the development of targeted drug delivery systems, including smart drug delivery systems that can be programmed to release drugs in response to tumor-specific stimuli, including enzymatic activity, acidic pH, temperature, or external stimuli, including light, ultrasound, or magnetic fields. The integration of AI modeling with these precision delivery methods is further advancing the strategies aimed at improving the accumulation of anticancer therapeutics at the tumor site while minimizing the systemic toxicity of the treatment. The review also highlights the recent advances of various ligand-mediated targeting strategies that include antibodies, peptides, aptamers, proteins, and small molecule ligands, as well as the application of AI modeling for improving the nanoparticle-based treatment regimens. Overall, these advances are further propelling the development of highly personalized treatment strategies that are effective against cancer. The further integration of these computer modeling tools with the cutting-edge biomaterials technology is expected to show great promise for improving the treatment of cancer while bypassing the TME-mediated barriers.
Unraveling the Complex Roles of Uric Acid in Autoimmune Diseases: Insights into Pathogenesis and Therapeutic Potential.
Gao YC, Hu X, Li WJ … +3 more , Wang DG, Pan HF, Wang P
Curr Pharm Des · 2026 May · PMID 42136503 · Publisher ↗
Uric Acid (UA), a weak acid and the final metabolite of purine degradation, exists in two primary forms in vivo: soluble UA (sUA) and Monosodium Urate (MSU) crystals. It is predominantly excreted through urine after the...
Uric Acid (UA), a weak acid and the final metabolite of purine degradation, exists in two primary forms in vivo: soluble UA (sUA) and Monosodium Urate (MSU) crystals. It is predominantly excreted through urine after the catabolism of adenine and guanine, maintaining a dynamic equilibrium within physiological conditions. UA exhibits notable antioxidant properties that contribute to the maintenance of redox homeostasis and the modulation of immune responses. However, disruptions caused by diet, lifestyle, or metabolic abnormalities can disturb UA equilibrium, resulting in oxidative imbalance, immune dysregulation, and chronic inflammation. Autoimmune Diseases (ADs) arise from a breakdown of immune tolerance, leading to the activation of autoreactive T and B cells, excessive autoantibody formation, dysregulated cytokine networks, and sustained tissue-damaging inflammation. Emerging evidence has unveiled that UA may trigger and participate in the onset and progression of several types of ADs by initiating oxidative stress (OS), modulating immune responses, and amplifying inflammatory mediators. In this review, summarize current advances in understanding the immunological roles of UA in the initiation and progression of ADs. We also evaluate the clinical relevance of UA as an immunomodulatory biomarker and therapeutic target. Furthermore, we explore conventional therapeutic approaches for ADs in combination with UA-lowering interventions, aiming to identify optimized treatment strategies tailored to specific autoimmune conditions to improve clinical outcomes.
RNA Interference-based Alternatives in the Control and Treatment of Neglected Tropical Diseases: A Systematic Review.
de Melo DF, Alves Júnior JO, Bezerra BMS … +3 more , Rillo Sato M, Rolim Neto PJ, Oshiro-Junior JA
Curr Pharm Des · 2026 May · PMID 42136502 · Publisher ↗
INTRODUCTION: Advances in scientific research have enabled gene modification in living organisms. RNA interference (RNAi) has become a preferred method for targeted gene silencing in the treatment of diseases caused by i...
INTRODUCTION: Advances in scientific research have enabled gene modification in living organisms. RNA interference (RNAi) has become a preferred method for targeted gene silencing in the treatment of diseases caused by infectious agents. In particular, neglected tropical diseases (NTDs) may benefit from RNAi approaches, as their causative organisms often present complex life cycles, offering multiple developmental stages that can be targeted to interrupt disease progression. This review systematically compiles and integrates studies on the application of RNAi, especially small interfering RNA (siRNA), in NTDs, highlighting its effectiveness through in vitro and in vivo evidence. METHODS: Four bibliographic databases, Science Direct, PubMed, CAPES Journals, and Web of Science, were used to search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines. RESULTS: A total of 4559 articles, from which 61 were selected. The main diseases found were schistosomiasis, malaria, filariasis, leishmaniasis, and Chagas disease. DISCUSSION: The integration of the studies demonstrated that RNAi is applied both to the parasite, compromising its behavior, structure, and functional development, and to intermediate and final hosts, to prevent parasitism and proliferation. Nevertheless, translational limitations and the route of administration must be considered, for instance. CONCLUSION: Thus, although the application of RNAi is promising for the treatment of NTDs, studies are needed to elucidate safe and effective delivery mechanisms, as well as to encourage research into the treatment of NTDs using new therapies that are not entirely drug-based.
Recent Advances in Pectin-Based Materials for Therapeutic Applications: A Review.
Felemban MF, Ashour AA, Tayeb FJ … +1 more , Shafie A
Curr Pharm Des · 2026 May · PMID 42136501 · Publisher ↗
Pectin, a naturally derived biopolymer, has emerged as a versatile material in pharmaceutical and biomedical research due to its solubility, biocompatibility, biodegradability, and gelling properties. Its nontoxic nature...
Pectin, a naturally derived biopolymer, has emerged as a versatile material in pharmaceutical and biomedical research due to its solubility, biocompatibility, biodegradability, and gelling properties. Its nontoxic nature and hydrogel-forming ability facilitate the encapsulation and controlled release of bioactive compounds, making it a promising platform for targeted drug delivery. Recent studies have demonstrated that chemical modifications of pectin, such as esterification, amidation, and graft copolymerization, significantly enhance its physicochemical and functional properties, enabling the design of advanced therapeutic systems. Pectin-based materials have been shown to improve drug stability, bioavailability, and site-specific delivery, particularly in anticancer, antidiabetic, and antimicrobial applications. Additionally, in vitro and in vivo studies indicate that pectin exhibits intrinsic biological activities, including antioxidant, anti-inflammatory, antihypertensive, and neuroprotective effects, further supporting its therapeutic potential. This review provides a comprehensive analysis of recent advancements in pectin-based materials from 2021 to 2025, with a focus on their applications in medicinal chemistry. It examines the inherent physicochemical and biological properties of pectin that enable the design of multifunctional materials, particularly for controlled drug delivery. Furthermore, the review highlights the diverse therapeutic activities of pectin-based systems, including anticancer, antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and many other activities, emphasizing their potential for developing innovative biomedical applications.
Group 3 Innate Lymphoid Cells (ILC3s): A Promising Immune Cell Group as Therapeutic Targets for Sjögren's Syndrome.
Wu Y, Liu J, Liu G … +3 more , Chu T, Yan X, Fang W
Curr Pharm Des · 2026 May · PMID 42136500 · Publisher ↗
Sjögren's syndrome (SS) is a chronic autoimmune disease primarily characterized by dry mouth and dry eyes, and its pathogenesis remains incompletely understood. Group 3 innate lymphoid cells (ILC3s), which are distribute...
Sjögren's syndrome (SS) is a chronic autoimmune disease primarily characterized by dry mouth and dry eyes, and its pathogenesis remains incompletely understood. Group 3 innate lymphoid cells (ILC3s), which are distributed throughout the intestinal and respiratory mucosa, secrete cytokines such as interleukin (IL)-22 and IL-17, which are critical for maintaining tissue homeostasis and modulating inflammatory responses. Emerging evidence from immunofluorescence analyses reveals that in the salivary glands of SS patients, ILC3s constitute the predominant innate lymphoid cell population (approximately 95.8%) and are significantly enriched within lymphocytic infiltrates compared to controls. Additionally, how functional alterations of ILC3s and their interactions with the gut microbiota contribute to intestinal dysfunction in SS remains to be investigated. This article aims to review the role of ILC3s in SS and to explore the underlying mechanisms involved, thereby providing insights for future research into disease pathogenesis and potential therapeutic targets.
Phytochemical and Pharmacological Insights into Barleria Prionitis L., Barleria Cristata L., and Barleria Lupulina Lindl: A Global Perspective on Medicinal Potential.
Bhardwaj A, Das R, Aggarwal A … +2 more , Sharma V, Mehta DK
Curr Pharm Des · 2026 May · PMID 42136499 · Publisher ↗
INTRODUCTION: Medicinal plants remain central to global healthcare systems, particularly in countries such as India, which is recognized for its rich diversity of therapeutic botanicals. The genus Barleria, belonging to...
INTRODUCTION: Medicinal plants remain central to global healthcare systems, particularly in countries such as India, which is recognized for its rich diversity of therapeutic botanicals. The genus Barleria, belonging to the family Acanthaceae, comprises over 300 species and represents the third largest genus within the family. Among these, Barleria prionitis Linn., Barleria cristata Linn, and Barleria lupulina Lindl are extensively studied due to their diverse phytochemical profiles and notable medicinal potential. METHODS: This structured review synthesizes literature published between 1990 and 2025 on the medicinal relevance of the selected Barleria species. A comprehensive search was conducted using major scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. Keywords such as "phytochemistry," "traditional uses," and "pharmacological activities" guided article selection, focusing on peer-reviewed studies addressing phytochemical composition and biological activities. RESULTS: Phytochemical investigations reveal that these species are rich in terpenoids, iridoid glycosides, flavonoids, phenolic acids, and essential oils. These bioactive constituents demonstrate broad pharmacological properties, including antibacterial, anti-inflammatory, antioxidant, antifungal, antidiabetic, hepatoprotective, neuroprotective, immunomodulatory, cardioprotective, and anticancer effects. DISCUSSION: The diverse phytochemical spectrum underpins the wide-ranging therapeutic activities of these plants, validating their traditional uses and supporting their relevance in contemporary pharmacological research. CONCLUSION: The review highlights the ethnopharmacological importance of Barleria species and underscores their promise as sources for novel drug development, providing a foundation for future scientific and pharmaceutical exploration.
Discovering Novel Drug Targets in Clostridioides difficile and Proposing FtsZ Inhibitors via Structure-Based Virtual Screening.
Sholeh M, Beig M, Moradkasani S … +2 more , Lopes BS, Badmasti F
Curr Pharm Des · 2026 May · PMID 42136498 · Publisher ↗
INTRODUCTION: Clostridioides difficile is a major healthcare-associated pathogen causing severe diarrhea and recurrent infections, particularly in older adults. With rising antibiotic resistance, identifying novel drug t...
INTRODUCTION: Clostridioides difficile is a major healthcare-associated pathogen causing severe diarrhea and recurrent infections, particularly in older adults. With rising antibiotic resistance, identifying novel drug targets and inhibitors is crucial for effective therapeutic intervention. METHODS: A two-phase in silico approach identified potential drug targets from C. difficile strain 630. Complete protein sequences were retrieved from NCBI, with high-prevalence proteins identified using EDGAR and essential cytoplasmic proteins determined through PSORTb. Proteins homologous to the human proteome and gut microbiota were excluded. The filamenting temperature-sensitive mutant Z (FtsZ) protein was selected for structure-based virtual screening using the AlphaFold-generated model. Molecular docking simulations were performed on StreptomeDB compounds using AutoDock Vina, followed by molecular dynamics simulations. Binding affinity, Lipinski's Rule of Five compliance, and ADMET properties were evaluated. RESULTS: Six promising drug targets were identified: nusG, nusA, accB, argB, ftsZ, and aroE. Virtual screening against FtsZ revealed 27 high-affinity ligands, with fasamycin C and formicamycin D demonstrating favorable profiles. Molecular dynamics simulations confirmed FtsZ-ligand complex stability. DISCUSSION: Identification of FtsZ as a drug target with fasamycin C and formicamycin D as promising inhibitors offers potential solutions for C. difficile infections amid escalating antibiotic resistance. This computational approach enhances antimicrobial drug discovery efficiency. CONCLUSION: This study identified six drug targets for C. difficile, with FtsZ emerging as a promising therapeutic candidate. Fasamycin C and formicamycin D exhibited strong binding affinity and favorable drug-like properties. In vitro and in vivo validation is essential to translate these findings into viable therapeutic options.
Plant-Derived Phytochemicals and Polyherbal Formulations in Antimicrobial Resistance: Mechanistic Evidence, Evidence Hierarchy, and Translational Constraints.
Ahirwar H, Singhai H, Rathee S … +3 more , Soni S, Gupta A, Patil UK
Curr Pharm Des · 2026 May · PMID 42136497 · Publisher ↗
The increasing global burden of antimicrobial resistance (AMR) has stimulated renewed interest in plant-derived phytochemicals and polyherbal formulations as potential adjuncts to conventional antimicrobial therapy. This...
The increasing global burden of antimicrobial resistance (AMR) has stimulated renewed interest in plant-derived phytochemicals and polyherbal formulations as potential adjuncts to conventional antimicrobial therapy. This article presents a narrative review, supported by a structured literature search, that synthesizes mechanistic and translational evidence on plant-based strategies targeting resistant bacterial pathogens. Literature was identified through searches of major scientific databases, including PubMed, Scopus, and Web of Science, with emphasis on studies published over the past two decades. Evidence is critically organised according to experimental level, distinguishing in vitro findings, in vivo observations, and available clinical data. Plant-derived compounds, including alkaloids, flavonoids, terpenoids, phenolics, and saponins, exhibit diverse antimicrobial and antibiofilm activities. Reported mechanisms include membrane disruption, inhibition of quorum sensing and biofilm formation, interference with nucleic acid and protein synthesis, modulation of efflux pumps, and attenuation of resistance-associated pathways. While reproducible antibacterial activity is frequently observed under laboratory conditions, animal studies remain limited, and robust clinical trials are scarce. Polyherbal formulations derived from traditional medical systems propose multi-target synergistic effects; however, pharmacodynamic validation and dose standardization remain insufficient. Key translational challenges include variability in extract composition, incomplete pharmacokinetic and pharmacodynamic characterization, limited bioavailability, potential toxicity, and clinically relevant herb-drug interactions. Many antimicrobial effects reported in vitro occur at concentrations that have not yet been demonstrated to be achievable or safe in humans. Emerging approaches such as nano-enabled delivery systems and omics-guided phytochemical characterisation may improve therapeutic precision but require rigorous validation. Overall, plant-derived products are best positioned as adjunctive resistance-modifying strategies rather than replacements for conventional antibiotics, pending standardised development and high-quality clinical evaluation.
Exploring the Antimicrobial Potential of Spirocyclic Compounds: A Comprehensive Review.
Alghannam D, Morsy MA, Tratrat C … +9 more , Acharya R, Gupta G, Tiwari V, Mahomoodally MF, Attimarad M, Nagaraja S, Mohanlall V, Venugopala KN, Deb PK
Curr Pharm Des · 2026 May · PMID 42136496 · Publisher ↗
INTRODUCTION: The global increase in antimicrobial resistance presents a significant public health challenge and calls for the discovery of new antimicrobial agents with innovative mechanisms of action. Spirocyclic compo...
INTRODUCTION: The global increase in antimicrobial resistance presents a significant public health challenge and calls for the discovery of new antimicrobial agents with innovative mechanisms of action. Spirocyclic compounds, characterized by two or more rings connected via a single shared atom, have attracted interest due to their rigid three-dimensional structures and promising pharmacological activities. This review aims to summarize research published between 2019 and 2025 on the antibacterial potential of natural, semisynthetic, and synthetic spirocyclic compounds, emphasizing their activity against Gram-positive, Gramnegative, and resistant bacterial strains. It also highlights promising therapeutic scaffolds and explores Structure- Activity Relationships (SAR) where available. METHODS: Relevant literature was gathered from peer-reviewed scientific databases. Studies reporting antibacterial evaluations of spirocyclic derivatives were included. Reported compounds were classified based on their core scaffold type, and their antibacterial activities, synergistic effects with standard antibiotics, and insights from computational docking were examined. RESULTS: Several spirocyclic scaffolds demonstrated antibacterial potential, including spiro β-lactams, spiro chromanes, spiro thiazolidines, and especially spiro oxindoles, which were the most extensively studied (44 research articles). Many compounds showed notable antibacterial activity against drug-resistant strains, and synergistic effects were observed when combined with conventional antibiotics. One spiro pyrimidinetrione derivative was approved recently by the US FDA, indicating translational potential. Molecular docking studies supported mechanistic understanding by predicting possible bacterial targets. DISCUSSION: Due to their wide applications across various scaffolds, spiro frameworks could be a valuable strategy in defeating bacteria. This architecture offers structurally unique compounds by expanding the threedimensional chemical space that may address antimicrobial resistance. Further exploration through Mechanistic validations and systematic structure-activity relationships studies is required to fully understand the potential of spiro compounds. CONCLUSION: Spirocyclic compounds are a valuable class of antibacterial agents owing to their structural diversity and efficacy. This review offers insights into their therapeutic potential and provides a foundation for future drug development targeting antimicrobial resistance.
Perspectives on 3D-printed Tablets for Drug Release Systems.
Moreira da Silva CDC, do Nascimento T, Lifsitch Viçosa A … +5 more , Hecht Ortiz B, Lopes Gama E Silva G, Sato de Souza de Bustamante Monteiro M, Dos Santos Matos AP, Ricci-Junior E
Curr Pharm Des · 2026 May · PMID 42136495 · Publisher ↗
INTRODUCTION: Oral solid pharmaceutical forms, such as tablets, are the most produced and consumed medicines due to their advantages in transportation and administration. However, they are manufactured on an industrial s...
INTRODUCTION: Oral solid pharmaceutical forms, such as tablets, are the most produced and consumed medicines due to their advantages in transportation and administration. However, they are manufactured on an industrial scale, generating thousands of units in a brief period, not allowing for dose flexibility or customization. 3D printing of medicines is a trend that has been growing worldwide to fill this treatment gap, favoring personalized treatment. To perform an integrative literature review, only research articles were considered. The aim was to map and analyze the current landscape of drug delivery systems developed through 3D printing technologies. METHODS: Bibliometric analysis was conducted using three databases, Science Direct, Springer, and PubMed, from January 2013 to May 2025, and only research articles were considered. RESULTS: The article is an integrative literature review considering only research articles, articles published (no preprint format is considered), and articles focusing on the pharmaceutical, toxicological, and pharmacological sciences areas. DISCUSSION: Among the studies included, FDM was the predominant 3D printing technique, and prolongedrelease tablets were the most frequently reported systems. Drug release was mainly governed by polymer type, printing method, and tablet design. CONCLUSION: 3D printing offers a versatile approach for tailoring drug release in oral dosage forms, with strong potential for personalized medicine, although broader exploration of alternative printing techniques and translational studies is still needed. More studies involving the quality control of 3D tablets and the influence of printing parameters and in vivo behavior are needed to develop future medicines.
Smart Nanostructures in Oncology: Revolutionising Drug Delivery and Diagnostics.
Singh H, Tyagi U, Kumar A … +8 more , Anand A, Singh I, Sanshita, Mishra AK, Kumar A, Amin R, Sarma MK, Chopra H
Curr Pharm Des · 2026 May · PMID 42136494 · Publisher ↗
Cancer continues to pose a significant global health concern, requiring creative strategies to improve treatment results and diagnostic methods. Smart nanostructures represent a paradigm shift in cancer management, offer...
Cancer continues to pose a significant global health concern, requiring creative strategies to improve treatment results and diagnostic methods. Smart nanostructures represent a paradigm shift in cancer management, offering precision, efficiency, and multifunctionality. This review delves into the transformative role of smart nanostructures in oncology, emphasizing their potential to address critical limitations of conventional therapies, like systemic toxicity, drug toxicity, suboptimal targeting, and drug resistance. The diversity of smart nanostructures, including polymeric nanoparticles, liposomes, dendrimers, metal-based nanostructures, and carbon-based materials, is explored, highlighting their unique properties and applications. Stimuli- responsive nanostructures capable of modulating drug release under specific pH, temperature, redox, or enzymatic conditions are discussed as pivotal innovations for precise cancer therapy. Strategies for enhanced targeting, encompassing passive mechanisms such as the Enhanced Permeability and Retention (EPR) effect and active targeting through ligand-receptor interactions, highlight the significance of tumor specificity. In addition to medication delivery, the utilization of nanostructures in cancer diagnosis, such as imaging modalities, biomarker detection, and real-time observation, is examined. The advent of multifunctional theranostic platforms, integrating diagnostics and therapy, exemplifies the convergence of nanotechnology and oncology. Additionally, the review addresses the role of personalized medicine, leveraging patient-specific genomic and proteomic data to tailor nanostructure design. Emerging trends in fabrication techniques and the translation of nanostructures from laboratory research to clinical practice are critically assessed, offering insights into future opportunities and challenges. This comprehensive review seeks to offer a comprehensive knowledge of smart nanostructures that could transform cancer management.
Disruption of HOX Gene Regulation by Bisphenol A and Its Analogs: Epigenetic and Molecular Insights in Developmental Toxicity.
Salve YM, Bhalkar DB, Goyal SN
Curr Pharm Des · 2026 May · PMID 42136493 · Publisher ↗
INTRODUCTION: Bisphenol A (BPA), Bisphenol S (BPS), and Bisphenol F (BPF) are industrial chemicals with proven endocrine-disrupting activity. BPA, BPS, and BPF have estrogen-like activity and affect hormone action, leadi...
INTRODUCTION: Bisphenol A (BPA), Bisphenol S (BPS), and Bisphenol F (BPF) are industrial chemicals with proven endocrine-disrupting activity. BPA, BPS, and BPF have estrogen-like activity and affect hormone action, leading to developmental toxicity. Recent data have proven that BPA, BPS, and BPF affect Homeobox (HOX) gene expression, which is crucial for development and organogenesis. METHODS: An extensive literature survey was conducted using Google Scholar and PubMed, including literature published until 2025. The literature search was performed using various keywords like "Bisphenol A," "Bisphenol F," "Bisphenol S," "homeobox genes," "epigenetic regulation," and "developmental toxicity". RESULTS: From the literature survey, it was clearly proven that BPA and its derivatives have a high impact if exposed during fetal development. Epigenetic changes in HOX gene clusters, changes in histone modification patterns, and increased oxidative stress levels are major areas of concern regarding developmental toxicity, which can affect fetal development, including neural development, sexual differentiation, and bone formation, all of which are crucial for embryogenesis and organogenesis. DISCUSSION: The literature review revealed that BPA and its derivatives, though claimed to be safer, are as toxic as BPA and, in some instances, are even more toxic to the developing fetus. The mechanistic action of bisphenols and the dysregulation of HOX gene expression are important steps towards understanding the teratogenic potential of BPA and its derivatives. CONCLUSION: BPA, BPF, and BPS are major concerns for embryonic development, as these chemicals affect the regulation of HOX gene expression and the signaling pathways that are crucial for embryonic development. Regulatory action and the development of safer chemicals are important for the health and safety of the fetus and for reducing the potential for developmental hazards.
Overcoming Physiological Barriers in Brain Tumor Therapy: Advances in Nanomedicine, Ultramolecular Pharmaceuticals, and Targeted Drug Delivery.
Sharma S, Sharma R
Curr Pharm Des · 2026 May · PMID 42136492 · Publisher ↗
Targeting brain tumors remains a formidable challenge due to the presence of complex physiological barriers, notably the blood-brain barrier (BBB), the blood-brain tumor barrier (BBTB), and the nose- tobrain barrier. The...
Targeting brain tumors remains a formidable challenge due to the presence of complex physiological barriers, notably the blood-brain barrier (BBB), the blood-brain tumor barrier (BBTB), and the nose- tobrain barrier. These barriers hinder effective drug delivery, limiting therapeutic efficacy. This review provides a comprehensive analysis of the anatomical and molecular characteristics of these barriers, with particular emphasis on the heterogeneity of the BBTB and its implications for targeted drug transport. A detailed overview of various brain tumor types-including glioblastoma, pediatric brain tumors, and brain metastases-is presented alongside a critical evaluation of existing therapeutic modalities. The review highlights the advancement of ultramolecular pharmaceuticals specifically engineered to circumvent the BBTB, focusing on both transvascular and cell-mediated delivery mechanisms. The role of nanomedicine in modulating the immune response and altering the tumor microenvironment is explored as a promising avenue for enhancing therapeutic outcomes. Particular emphasis is placed on nanogels as a versatile and efficient drug delivery platform. Key fabrication techniques such as precipitation polymerization, emulsion polymerization, self-assembly, and micro-templating methods are thoroughly discussed, alongside strategies for polymer crosslinking to enhance stability and functionality. In addition, the review addresses preclinical evaluation strategies, including in vitro models (e.g., BBB-mimicking systems, tumor spheroids) and in vivo studies in animal models, to assess the safety, biodistribution, and therapeutic efficacy of nanogel-based systems. Finally, current clinical progress, challenges, and future perspectives are presented, underscoring the urgent need for innovative, targeted, and personalized drug delivery approaches. This review aims to guide future research in overcoming delivery obstacles and improving outcomes for patients with brain tumors through the strategic integration of advanced nanotechnology and molecular targeting.
Unlocking the Anticancer Potential of Umbelliprenin and Auraptene: A Comprehensive Review of Mechanisms and Efficacy Across Multiple Malignancies.
Mirjalili ES, Mohammadi-Zarch SM, Bagheri SM
Curr Pharm Des · 2026 May · PMID 42136491 · Publisher ↗
Cancer remains a leading cause of mortality worldwide, with conventional treatments like chemotherapy and radiotherapy often causing significant side effects. Natural compounds, such as Umbelliprenin (UMB) and Auraptene...
Cancer remains a leading cause of mortality worldwide, with conventional treatments like chemotherapy and radiotherapy often causing significant side effects. Natural compounds, such as Umbelliprenin (UMB) and Auraptene (AUR) from the Ferula genus, have shown promising anticancer properties with reduced toxicity. This review compares their efficacy against various cancers, focusing on their mechanisms and potency. Relevant studies were retrieved from databases including PubMed, Scopus, and Web of Science until the end of February 2025. Articles were screened by two independent researchers, excluding studies with synthetic modifications. Key findings on UMB and AUR's anticancer effects were analyzed and summarized. Both UMB and AUR exhibit significant anticancer effects across multiple cancer types, including breast, colon, gastric, lung, and others. UMB inhibits tumor growth by inducing apoptosis, arresting the cell cycle, and modulating pathways such as Wnt, NF-κB, and PI3K/Akt. It shows moderate potency (average IC50: 314 μM in breast cancer). AUR demonstrates higher potency (average IC50: 85.2 μM in breast cancer), targeting apoptosis, angiogenesis, and metastasis via pathways such as AMPK, mTOR, and ROS modulation. AUR also enhances chemoradiotherapy sensitivity and inhibits cancer stem cell markers. UMB and AUR are promising natural anticancer agents, with AUR showing superior potency, particularly in breast cancer, due to lower IC50 values and broader mechanistic effects. Further research is needed to optimize their delivery and clinical application.
Animal-Based Oils: Exploration of Their Nutritional and Medicinal Benefits.
Shinde SG, Thomas A, Deshkar S … +6 more , Kothapalli L, Thakre K, Borhade T, Chitlange S, Sanap A, Bhonde R
Curr Pharm Des · 2026 May · PMID 42136490 · Publisher ↗
This comprehensive review explores the properties and applications of natural oils derived from diverse animal sources. Fish-based supplements are today widely consumed for their nutritional/health benefits. In this cont...
This comprehensive review explores the properties and applications of natural oils derived from diverse animal sources. Fish-based supplements are today widely consumed for their nutritional/health benefits. In this context, this review opens doors to lesser-known oils that can be explored for such properties. Focusing on the nutritional spectra of omega-3 and omega-6 essential fatty acids, the document highlights the well-established benefits of fish oil, particularly for cardiovascular health. Further, little-known animalderived oils, including emu, crocodile, ostrich, cobra, and krill oils, are being studied for their unique chemical compositions and potential health benefits. These oils exhibit wound-healing (for burns and diabetic wounds), anti-inflammatory, anti-arthritic, and antimicrobial activities, and are used in the treatment of chemotherapy- induced mucositis and hyperlipidemia. Attempts are also made to understand the mechanistic pathways and signal modulations that contribute to the beneficial properties of these oils. Presently, the effective utilization of these oils in the mainstream is limited and underutilized. As our dependence on plant-based products increases, questioning their sustainability, lesser-known natural oils obtained through the processing of waste animal fats can be effectively employed, harnessing newer alternatives in nutrition, medicine, and therapeutics.
Curcumin and Its Nanoformulations: Emerging Strategies for the Prevention and Management of Allergic Diseases.
Marouzi S, Anbiaee G, Ansari B … +1 more , Hashemi M
Curr Pharm Des · 2026 May · PMID 42136489 · Publisher ↗
Allergic diseases are a heavy clinical and socioeconomic burden to human society. Dysregulated immune responses, especially a Th2 cytokine response and IgE-mediated hyperinflammation, are the main factors of the cascade...
Allergic diseases are a heavy clinical and socioeconomic burden to human society. Dysregulated immune responses, especially a Th2 cytokine response and IgE-mediated hyperinflammation, are the main factors of the cascade of cellular and molecular events that underlie the immunopathogenesis of allergic diseases. The traditional antiallergic treatment is restricted today because of a wide variety of adverse effects (skin atrophy, growth retardation in children, hypertension, osteoporosis, and tachycardia). Thus, preclinical research should find other interventions that have fewer side effects and optimize the effectiveness of the treatment plan. Curcumin is a polytropic bioactive polyphenol derived from the rhizome of turmeric plant (strong anti-inflammatory, antioxidant, and immunomodulatory properties). The low water solubility, chemical instability, and rapid systemic metabolism have, however, limited its clinical use. Reportedly, nanotechnology has attempted to improve the pharmacokinetic and therapeutic targeting of nanocurcumin formulations using a number of methods. Therefore, this paper is a review of the immunopharmacological prospects of curcumin and nanocurcumin in allergic diseases, including preclinical and clinical evidence. The current review paper reviews the effects of curcumin in the inhibition of Th2 responses. Moreover, it has explored the Th1/Th2 balance, mast cell degranulation inhibition, decreasing proinflammatory mediators, and immune modulation. Conversely, it has recommended nanotechnological methods to enhance the solubility, cellular internalization, and release characteristics of nanocurcumin preparations to increase its efficacy. Lastly, the review gives future research directions by ranking limitations of the existing literature (methodological diversity and difficulties in applying the results to a clinical setting).
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe