Med Chem [JOURNAL]
Sun
200 papers
Platinum Group Metals against Parasites: State of the Art and Future Perspectives.
Mendez-Arriaga JM
Med Chem · 2025 · PMID 39916434 · Publisher ↗
BACKGROUND: Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new...
BACKGROUND: Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new research lines, there has been a failure in the treatment of parasitic illnesses. OBJECTIVES: The present mini-review is a comprehensive review of the use of platinum group metals as biological agents. It aims to establish the actual state of the art of these metal elements in the antiparasitic activity-specific area and define the future possibilities of action. METHODS: The review comprises more than 100 research works done in this field. The differences between platinum group metals chemistry and their use as metal complexes with biological activity have been discussed. RESULTS: This review highlighted the platinum group metal's potential as an antiparasitic agent for different diseases. CONCLUSION: The review will be helpful for the researchers involved in targeted drugs for parasitic disease therapy.
Exploring Pyridine-Based Schemes: A Comprehensive Review on their Synthesis and Therapeutic Applications.
Balikai AM, Kumar MRP, Rajagopal K … +4 more , Alshehri MA, Obaidur Rab S, Nafady MH, Bin Emran T
Med Chem · 2026 · PMID 39878110 · Publisher ↗
Pyridine and its derivatives are six-membered aromatic rings containing nitrogen, which are abundant in nature and indispensable in studying heterocyclic chemistry. They constitute significant chemical substances with nu...
Pyridine and its derivatives are six-membered aromatic rings containing nitrogen, which are abundant in nature and indispensable in studying heterocyclic chemistry. They constitute significant chemical substances with numerous applications. The application of pyridine derivatives by incorporating metals in modern medicine is growing in relevance. Due to their convenient parallelization and various testing capabilities in the chemical domain, pyridine derivatives have attracted increased interest in the treatment of various disease states. This review aims to systematically evaluate and highlight the recent advancements in the synthesis (conventional, synthetic, and green approach) and biological activities of metal-based pyridine derivatives, including antioxidant, antimicrobial, and antitumor activities, while identifying promising candidates for further drug development. By consolidating all this knowledge underlying their biological effects, this review aims to pave the way for future research endeavors and encourage the exploration of pyridine derivatives as viable therapeutic agents across a diverse array of medical applications.
Integrating Machine Learning and Pharmacophore Features for Enhanced Prediction of H1 Receptor Blockers.
Sherwani ZA, Nur-E-Alam M, Ahmed A … +1 more , Ul-Haq Z
Med Chem · 2025 · PMID 39871575 · Publisher ↗
INTRODUCTION: Histamine Type I Receptor Antagonists (H1 blockers) are widely used to mitigate histamine-induced inflammation, particularly in allergic reactions. Histamine, a biogenic amine found in endothelial cells, va...
INTRODUCTION: Histamine Type I Receptor Antagonists (H1 blockers) are widely used to mitigate histamine-induced inflammation, particularly in allergic reactions. Histamine, a biogenic amine found in endothelial cells, vascular smooth muscle, bronchial smooth muscle, and the hypothalamus, plays a key role in these responses. H1 blockers are essential components of cough syrups and flu medications. They are classified into two generations: first-generation H1 blockers, which are sedating and associated with numerous side effects, and second-generation blockers, which are non-sedating, generally less toxic, but may still exhibit cross-reactivity with other receptors. METHODS: In this study, a comprehensive database of compounds was utilized, with fexofenadine serving as a benchmark to discover compounds with potentially superior efficacy and reduced side effect profiles. In particular, multidimensional K-means clustering, a machine-learning technique, was applied to identify compounds with chemical structures similar to fexofenadine. RESULTS: Utilizing computational prediction of pharmacokinetic profile and molecular docking experiments, the action of these drugs on the H1 receptor was assessed. Furthermore, the crossreactivity of antihistamines was investigated by conducting a structure-based pharmacophore feature analysis of the docked poses of highly toxic antihistamines with various receptors. CONCLUSION: By identifying and proposing the removal of common toxic features, this study aims to facilitate the development of antihistamines with reduced adverse effects.
Pyridine Derivatives: A Comprehensive Review of Their Potential as Anti-Diabetic Agents.
Dua D, Kumar P, Anand R … +2 more , Sood S, Singh G
Med Chem · 2025 · PMID 39865814 · Publisher ↗
BACKGROUND: Diabetes mellitus and obesity are two of the most frequent health conditions in the world, prompting medical researchers to seek novel effective treatments. According to World Health Organization (WHO) regula...
BACKGROUND: Diabetes mellitus and obesity are two of the most frequent health conditions in the world, prompting medical researchers to seek novel effective treatments. According to World Health Organization (WHO) regulations and several research studies, diabetes is regarded as a significant and leading health concern worldwide. The search for efficient and safe antidiabetic drugs has led to the study of pyridine derivatives, a family of molecules with a wide range of pharmacological characteristics. Pyridines are important heterocyclic chemicals renowned for their various pharmacological properties. METHODS: Materials were compiled using the three databases of ScienceDirect, PubMed, and Google Scholar. For this study, only English-language publications have been evaluated based on their titles, abstracts, and full texts using keywords like diabetes, pyridine Derivatives, α- glucosidase inhibitors, and α-amylase inhibitors. RESULTS: Pyridine and its derivatives have received a lot of attention due to their wide range of potential uses in medicinal chemistry and pharmacology. Structural alterations and optimization efforts have resulted in higher effectiveness, selectivity, and safety characteristics. These discoveries highlight the importance of pyridine analogues as a novel class of therapeutic agents for diabetes management. CONCLUSION: The review highlights the significance of pyridine analogues in the development of antidiabetic treatments, opening new avenues for developing drugs and clinical use. The ongoing advancements in the discovery of pyridine derivatives underscore their potential as prospective agents in diabetic treatments.
A Comprehensive Review: Synthesis and Pharmacological Activities of 1,3,4-Oxadiazole Hybrid Scaffolds.
Lata S, Choudhary L, Bharwal A … +2 more , Pandit A, Abbot V
Med Chem · 2025 · PMID 39851119 · Publisher ↗
INTRODUCTION: Heterocyclic derivatives, particularly those containing heteroatoms such as oxygen and nitrogen, represent a significant portion of currently marketed drugs. Among these, the aromatic heterocycle 1,3,4-oxad...
INTRODUCTION: Heterocyclic derivatives, particularly those containing heteroatoms such as oxygen and nitrogen, represent a significant portion of currently marketed drugs. Among these, the aromatic heterocycle 1,3,4-oxadiazole, characterized by an N=C=O-linkage, stands out due to its remarkable biological activities. These activities include anti-inflammatory, anti-cancer, antioxidant, anti-tubercular, antiviral, anti-diabetic, and antibacterial effects. Notably, several commercially available medications, such as tiodazosin, raltegravir, zibotentan, and nesapidil, incorporate this structural motif. METHODS: This review compiles and analyzes existing synthetic methods for preparing 1,3,4- oxadiazole and its derivatives. By examining various synthetic routes and methodologies, the review provides a detailed overview of the strategies employed to generate these biologically active compounds. RESULTS: The review highlights the potential of 1,3,4-oxadiazole derivatives in addressing the toxicity, side effects, and drug resistance commonly associated with existing anticancer therapies. By combining the 1,3,4-oxadiazole moiety with other heteroatoms, novel hybrid derivatives have been synthesized, demonstrating enhanced pharmacological activities across various therapeutic areas. CONCLUSION: This comprehensive review offers valuable insights into the synthesis and pharmacological applications of 1,3,4-oxadiazoles. It serves as a crucial resource for researchers exploring the development of new therapeutic compounds, with the ultimate goal of improving public health. The review builds on existing literature from the last two decades to present an exhaustive examination of the potential of 1,3,4-oxadiazole derivatives in drug development.
Exploring 1-Azaaurones: A Concise Overview of Synthetic Strategies and Biological Activities.
Chauhan N, Kumar S
Med Chem · 2025 · PMID 39851118 · Publisher ↗
Azaaurones are formed by the replacement of intra-cyclic oxygen of the central core of a five-membered furan ring or any other carbon of aurones by a nitrogen atom. However, 1- azaaurone obtained by the replacement of in...
Azaaurones are formed by the replacement of intra-cyclic oxygen of the central core of a five-membered furan ring or any other carbon of aurones by a nitrogen atom. However, 1- azaaurone obtained by the replacement of intra-cyclic oxygen is the most prominent and desirable. They are the bioactive compounds acting as potential anti-inflammatory, anticancer, antibacterial, and antiviral agents. They comprise relatively less explored, pharmacologically active compounds exhibiting diverse biological activities that can act as potential lead compounds in the context of drug development. This review represents a comprehensive and updated overview of the synthetic protocols and biological activities of 1-azaaurones and their derivatives, enabling the readers to know about the vast medicinal potential of azaaurones and their derivatives in different areas and prompt the medicinal chemists to emphasize their further exploration. Furthermore, this review also covers some important Structure-Activity Relationships (SAR), highlighting the most potential compounds in each series, providing pivotal scope for further improvisation.
Effective Synthesis of Dopamine Dimer.
Dejun Z, Yuying Z, Xiaoyue L … +1 more , Huachuan Z
Med Chem · 2026 · PMID 39851117 · Publisher ↗
BACKGROUND: Dopamine (1) is a commonly used vasopressor, primarily employed to treat various types of shock, congestive heart failure, and acute renal failure. Dopamine dimer (2) is an impurity generated during the produ...
BACKGROUND: Dopamine (1) is a commonly used vasopressor, primarily employed to treat various types of shock, congestive heart failure, and acute renal failure. Dopamine dimer (2) is an impurity generated during the production process of dopamine raw materials or the metabolism of dopamine drugs themselves. METHODS: This article presents an effective method for synthesizing dopamine dimer through the condensation of methyl 3,4-dimethoxyphenyl acetate (4) and 3,4-dimethoxyphenylethyl amine (5), followed by reduction and demethylation. RESULTS: The product was synthesized from easily accessible raw materials, achieving a total yield of 48% over five steps. CONCLUSION: This synthesis method is simple and beneficial for pharmaceutical companies to adopt and implement.
Synthetic Strategies for the Development of Novel Heterocycles as Larvicides Targeting Linn.
Brito TB, Oliveira LMS, Nunes RKV … +2 more , Maistro EL, de Holanda Cavalcanti SC
Med Chem · 2025 · PMID 39851116 · Publisher ↗
BACKGROUND: Owing to their extensive utilization as pesticides, heterocycles assume a fundamental role in the management of vector-borne diseases. Despite the presence of numerous heterocyclic compounds in commercial ins...
BACKGROUND: Owing to their extensive utilization as pesticides, heterocycles assume a fundamental role in the management of vector-borne diseases. Despite the presence of numerous heterocyclic compounds in commercial insecticides and larvicides, resistance to pesticides still demands novel strategies to current pest control methods. Considering these facts, this review aims to survey the synthesis and SAR of heterocyclic molecules with larvicidal activity against Linn. METHODS: Comprehensive searches across the major databases were conducted to identify heterocyclic compounds exhibiting larvicidal efficacy against with the goal to unveil the main characteristics that are essential for exhibiting larvicidal activity. RESULTS: Active compounds display LC values varying from 0.36 to 2907 µM. Fifteen heterocyclic compounds displayed larvicidal activities below 20 µM. Five-membered ring molecules containing nitrogen and oxygen have displayed larvicidal activity according to the position of heteroatoms in the ring. Molecules bearing 1,2,4-oxadiazole and 1,2-oxazole moieties have been shown to be more active than 1,3,4-oxadiazole derivatives. Compounds possessing the indole scaffold have proven to be more potent than isatin and pyrimidine derivatives. Structural characteristics other than a heterocyclic moiety, such as the presence of halogens and less ionized and polar molecules, may also play a role in determining the final larvicidal activity. CONCLUSION: The rationale behind this review is to stimulate the discovery of innovative heterocyclic larvicides. Thus, it is important to continue synthesizing new scaffolds to comprehensively elucidate the structure-activity relationship for each heterocyclic moiety outlined in this investigation..
Advances in Structural Types and Pharmacochemistry of CDK12 Inhibitors.
Wang D, Xia MT, Yan JX … +2 more , Yu L, Li S
Med Chem · 2025 Jan · PMID 39851115 · Publisher ↗
Cyclin-Dependent Kinase (CDK) 12 is a member of the 20-membered CDK family (CDK1-20) and plays a vital role in regulating gene transcription, mRNA splicing, translation, cell cycle, and repair of DNA damage. CDK12 is an...
Cyclin-Dependent Kinase (CDK) 12 is a member of the 20-membered CDK family (CDK1-20) and plays a vital role in regulating gene transcription, mRNA splicing, translation, cell cycle, and repair of DNA damage. CDK12 is an emerging therapeutic target due to its role in regulating the transcription of DNA Damage Response (DDR) genes in Cyclin-Dependent Kinase (CDK). However, the development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13. So far, no CDK12 inhibitors approved by the US FDA have been found, and more novel CDK12 inhibitors have been reported for the treatment of prostate cancer, breast cancer, ovarian cancer, lung adenocarcinoma, stomach cancer, cervical cancer, etc. This review has attempted to summarize the structural characteristics and biological activities of various novel CDK12 inhibitors reported since 2020. Meanwhile, we collated and analyzed the reported CDK12 inhibitors from the perspective of structure, summarized the current clinical application potential of CDK12 inhibitors, and further analyzed their current challenges and future development trends.
Exploring the Therapeutic Potential of 1,3-Thiazole: A Decade Overview.
Manchare A, Parit S, Lele M … +1 more , Hatvate N
Med Chem · 2025 · PMID 39844396 · Publisher ↗
The escalating prevalence of lifestyle and microbial diseases poses a significant threat to human well-being, necessitating the discovery and development of novel drugs with distinct modes of action. Addressing this chal...
The escalating prevalence of lifestyle and microbial diseases poses a significant threat to human well-being, necessitating the discovery and development of novel drugs with distinct modes of action. Addressing this challenge involves employing innovative strategies, and one current approach involves utilizing heterocyclic compounds to synthesize hybrid molecules. These hybrids have resulted from the fusion of two or more bioactive heterocyclic moieties into a single molecule. The focus of this review revolves around the strategic incorporation of heterocycles, particularly thiazole derivatives. Thiazole derivatives, due to their unique structural features, are explored in depth within this review paper. The paper comprehensively outlines diverse hybridization strategies of thiazole derivatives, highlighting their vibrant biological activities mainly in the last decade, 2014-2024. By presenting an extensive overview, the review aims to provide valuable insights into the potential of thiazole derivatives as promising candidates for drug development. The insights garnered from this paper are expected to offer valuable guidance for future drug design endeavors, providing a foundation for developing novel and effective drugs to combat lifestyle diseases and microbial resistance.
Natural Compounds from as Potential HCC and HepG2 Inhibitors: An Integrated Study using Pharmacophore Development, Molecular Docking, MD Simulation, and DFT Approaches.
Moveed A, Parveen S, Shafiq N … +6 more , Ali A, Rashid M, Bourhia M, Msanda F, Salamatullah AM, Brogi S
Med Chem · 2025 · PMID 39838657 · Publisher ↗
BACKGROUND: The rise in the frequency of liver cancer all over the world makes it a prominent area of research in the discovery of new drugs or repurposing of existing drugs. METHODS: This article describes the pharmacop...
BACKGROUND: The rise in the frequency of liver cancer all over the world makes it a prominent area of research in the discovery of new drugs or repurposing of existing drugs. METHODS: This article describes the pharmacophore-based structure-activity relationship (3DQSAR) on the secondary metabolites of to inhibit human liver cancer cell lines Hepatocellular carcinoma (HCC) and hepatoma G2 (HepG2) which represents the molecular level understanding for isolated phytochemicals of . The definite features, such as hydrophobic regions, average shape, and active compounds' electrostatic patterns, were mapped to screen phytochemicals. The 3D-QSAR model generates pharmacophore-based descriptors and alignment of active compounds. Further, docking studies were performed on the active compounds to check out their binding affinity with the active site of the target proteins. It was further validated by applying molecular simulations, and the results were found to be accurate. The geometrical optimization and energy gap of the hit compound were calculated by the density functional theory (DFT). Then, ADMET was performed on this hit compound for drug-like features and toxicity. RESULTS: Out of 59 compounds, eight ligands were found active after the 3D-QSAR study. After that, molecular docking was performed on the active compounds F72, F52, F54, F29, F37, F38, F25, and F29, which were recognized as potential targets, and the docking results showed that compound F52 (also an FDA-approved drug) was the best hit. F52 was found to be the best hit against liver cancer cell lines HCC and HepG2. CONCLUSION: This study would be helpful for early drug discovery optimization and lead identification.
High-prediction QSAR Modeling Study Based on the Efficacy of a Novel 6-hydroxybenzothiazole-2-carboxamide Targeted Monoamine Oxidase B in the Treatment of Neurodegenerative Diseases.
Xie D, Cai Z, Mao J … +3 more , Qu X, Cao L, Zhou J
Med Chem · 2025 · PMID 39838656 · Publisher ↗
BACKGROUND: Neurodegenerative diseases are a group of disorders characterized by progressive neuronal degeneration and death, of which Alzheimer's disease and Parkinson's disease are the most common. These diseases are c...
BACKGROUND: Neurodegenerative diseases are a group of disorders characterized by progressive neuronal degeneration and death, of which Alzheimer's disease and Parkinson's disease are the most common. These diseases are closely associated with increased expression of monoamine oxidase B (MAO-B), an important enzyme that regulates neurotransmitter concentration, and its overactivity leads to oxidative stress and neurotoxicity, accelerating the progression of neurodegenerative diseases. Therefore, the development of effective MAO-B inhibitors is important for the treatment of neurodegenerative diseases. OBJECTIVE: This study aims to improve the prediction of the efficacy of novel 6-hydroxybenzothiazole- 2-carboxamide compounds in inhibiting MAO-B by improving the quantitative constitutive effect relationship (QSAR) modeling and to provide a theoretical basis for the discovery of novel neuroprotective drugs. METHODS: The study first optimized the structures of 36 compounds using the heuristic method (HM) in CODESSA software to construct linear QSAR models. Subsequently, key descriptors were screened by using the gene expression programming (GEP) technique to generate nonlinear QSAR models and validate them. RESULTS: The R², F-value, and R²cv of the linear model were 0.5724, 10.3752, and 0.4557, respectively, whereas the nonlinear model constructed by the GEP algorithm showed higher prediction accuracies by achieving R² values of 0.89 and 0.82, and mean squared errors (MSE) of 0.0799 and 0.1215 for the training and test sets, respectively. In addition, molecular docking experiments confirmed that the novel compound 31 was tightly bound to the MAO-B active site with significant inhibitory activity. CONCLUSION: In this study, we successfully improved the prediction ability of the efficacy of novel 6-hydroxybenzothiazole-2-carboxamide compounds to inhibit MAO-B by improving the QSAR model. This not only provides new drug candidates for the treatment of neurodegenerative diseases, but also provides important theoretical guidance for subsequent drug design and development, which can help accelerate the process of new drug discovery and reduce the disease burden of patients.
Recent Advancements in the Synthetic Chemistry of Oxazole Derivatives and their Significant Medicinal Applications.
Yadav P, Shah K
Med Chem · 2025 · PMID 39838655 · Publisher ↗
The five-membered oxazole motif heterocyclic aromatic ring has been gaining considerable attention due to its bioisosterism property and unusually wide range of desired biological properties. Thus, it is a perfect pre-bu...
The five-membered oxazole motif heterocyclic aromatic ring has been gaining considerable attention due to its bioisosterism property and unusually wide range of desired biological properties. Thus, it is a perfect pre-built platform for the discovery of new scaffold development in medicinal chemistry. In recent years, the potential of oxazoles has garnered significant attention from medicinal chemists, resulting in the development of several synthetic and plant-based drugs currently in the market. Interest in the biological applications of oxazoles has notably intensified over the past fifteen years. This overview aims to provide a comprehensive, systematic summary of recent advancements in the synthetic chemistry of oxazole-based compounds, highlighting significant progress in their biological applications during this period as well as outlining prospects for further development. In summary, we overview literature in synthetic chemistry and explore structure- activity relationships and mechanisms of action with medicinal applications for the development of oxazole derivatives that hold promise for discovering new and effective drug candidates.
Promising Anticancer Activity of Pyrazole Compounds against Glioblastoma Multiforme: Their Synthesis, , and Molecular Docking Studies.
Nalcı KA, Mete C, Demir Z … +2 more , Bildirici İ, Cetin A
Med Chem · 2025 · PMID 39835556 · Publisher ↗
BACKGROUND: Glioblastoma Multiforme (GBM), a highly aggressive and prevalent brain cancer with a higher incidence in males, has limited treatment success due to drug resistance, inadequate targeting and penetration of ca...
BACKGROUND: Glioblastoma Multiforme (GBM), a highly aggressive and prevalent brain cancer with a higher incidence in males, has limited treatment success due to drug resistance, inadequate targeting and penetration of cancer cells, and an incomplete understanding of its molecular pathways. GBM is a highly aggressive brain cancer with limited treatment options. This study investigates the anticancer potential of synthesized pyrazole compounds against GBM cells. METHODS: A series of pyrazole derivatives were synthesized and tested for their efficacy against GBM using MTT assays. Molecular docking studies were conducted to explore the binding interactions of these compounds with GBM receptors. RESULTS: Compounds 3 and 5 demonstrated significant anticancer activity, reducing cell viability more effectively than the control group. MTT assay results confirmed their potency. Molecular docking studies revealed strong binding interactions with GBM receptors, highlighting their potential as anticancer agents. CONCLUSION: The study evaluated the anticancer activity of synthesized compounds on human GBM cells, with compounds 3 and 5 showing the most promising results. Pyrazole 3 significantly reduced cell viability at high concentrations, while both pyrazoles 3 and 5 required higher doses to achieve substantial effects, as indicated by their IC values. Molecular docking studies confirmed strong binding interactions with the GBM receptor, and the pharmacokinetic properties suggest their potential as anticancer agents. These results highlight compounds 3 and 5 as candidates for further investigation.
An Integrative Computational Approach for the Identification of C-Abl Kinase Inhibitors from Anti-Parkinson Plant-Derived Bioactive.
Umar HI, Ashimiyu-Abdusalam Z, Kumar N … +8 more , Kuthi NA, Victor O, Abdulsalam ZN, Aribo EO, Bello RO, Bin Jardan YA, Nafidi HA, Bourhia M
Med Chem · 2025 · PMID 39812069 · Publisher ↗
BACKGROUND: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tR...
BACKGROUND: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α -synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential. Despite three generations of tyrosine kinase inhibitors (TKIs) being explored for PD treatment, they present significant concerns including poor blood-brain barrier penetration, off-target effects, and severe side effects. Notably, there are currently no FDA-approved c-Abl kinase inhibitors in clinical usage for PD treatment, highlighting the urgent need for potent, safe, and cost-effective alternatives. OBJECTIVE: This study aims to identify potential c-Abl kinase inhibitors from plant-derived compounds with reported anti-Parkinson's potential and their derivatives using molecular docking, molecular dynamics simulations (MDS), and in silico pharmacokinetics and toxicity profiling. METHODS: Seventy-eight compounds sourced from literature were docked against c-Abl kinase using Maestro 12.5. The top three hit compounds, along with nilotinib (control drug), were subjected to drug-likeness, ADMET profiling using the AI Drug Lab server and 100 ns MDS using Desmond. RESULTS: Amburoside A, diarylheptanoid MS13, and dimethylaminomethyl-substituted-curcumin showed binding affinities close to nilotinib, with values of -12.615, -12.556, and -11.895 kcal/mol respectively, compared to nilotinib's -16.826 kcal/mol. The three plant-derived compounds exhibited excellent structural stability and favorable ADMET profiles, including optimal blood-brain barrier permeation. CONCLUSION: The three hit compounds identified in this study show potential as c-Abl kinase inhibitors. Given the absence of FDA-approved c-Abl kinase inhibitors for PD, these findings are significant as they could contribute new therapeutic options for the treatment and management of PD. However, further and experiments are necessary to validate these findings.
Identification of Natural Terpenoid Compounds as Potential Inhibitors of Nucleoprotein of Influenza A Virus using Approach: ADMET, Molecular Docking, and Molecular Dynamic Simulation.
Hossain MS, Ali MM, Dey PR … +5 more , Khandocar MP, Haque SMJ, Bin Jardan YA, Ibenmoussa S, Bourhia M
Med Chem · 2025 · PMID 39812068 · Publisher ↗
BACKGROUND: We continue to struggle with the prevention and treatment of the influenza virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous fatalities. The threat of influenz...
BACKGROUND: We continue to struggle with the prevention and treatment of the influenza virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous fatalities. The threat of influenza remains a significant concern for global health, and the development of novel drugs targeting these viruses is highly desirable. OBJECTIVE: The objective of this study is to explore the inhibitory potential of terpenoid compounds against the Nucleoprotein (NP) of influenza A virus, which is a highly effective drug target due to its ability to facilitate the transcription and replication of viral RNA. METHODS: research was performed to identify potential inhibitors of NP. Molecular docking studies were conducted to assess the binding of terpenoid compounds to the active site residues of the target protein. The most promising hits were then subjected to molecular dynamics simulations to examine the stability of the protein-ligand complexes. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies and Lipinski's rule of five were employed to evaluate the drug safety and druglikeness of the compounds. RESULT: Docking studies revealed that the terpenoid compounds bind strongly to the active site residues of the NP protein. Molecular dynamics simulations demonstrated the stability of the proteinligand complexes for the best-hit compounds. ADMET studies and Lipinski's filter indicated that the compounds exhibit desirable drug safety and drug-likeness profiles. CONCLUSION: This work may contribute significantly to drug discovery and the development of therapeutic agents against the influenza A virus. The identification of terpenoid compounds that bind strongly to the NP protein and exhibit favorable drug-like properties through in silico studies provides a promising foundation for further research and the development of potential inhibitors targeting this critical viral protein.
Pyrazoline Derivatives: Exploring the Synthesis and Development of New Ligands for Anti-Cancer Therapy.
Sharma R, Salahuddin, Mazumder A … +6 more , Kumar R, Chauhan A, Ahsan MJ, Yar MS, Maqsood R, Singh S
Med Chem · 2025 · PMID 39806978 · Publisher ↗
Pyrazoline is a 5-membered ring that has two adjacent nitrogen. It has gained advanced attention from medical and organic chemists due to very low cytotoxic activities. It is applicable and more applied in research field...
Pyrazoline is a 5-membered ring that has two adjacent nitrogen. It has gained advanced attention from medical and organic chemists due to very low cytotoxic activities. It is applicable and more applied in research fields and has various pharmacological activities, including cardiovascular, anti-tumor, and anti-cancer properties. In this review, the main objective is to study the pharmacological aspects of pyrazoline and its derivative analogs. The present synthetic pyrazolines are better scaffolds, which show more biological and medicinal characteristics. These compounds exhibit diverse pharmacological activities, showcasing their potential as promising candidates for cancer therapy. Pyrazolines demonstrate remarkable anti-proliferative and apoptosis-inducing effects on cancer cells, attributed to their distinctive molecular structure. This review highlights the growing significance of pyrazolines in medicinal chemistry, emphasizing their role in designing novel anticancer agents. The multifaceted properties of pyrazolines offer a compelling foundation for further research, driving innovation in the quest for effective and targeted anticancer drugs.
Isoindoline-1,3-dione Derivatives as Prototypes for Anticonvulsant Drug Discovery.
Chelucci RC, Chiquetto R, Chiba DE … +3 more , Scarim CB, Chin CM, Dos Santos JL
Med Chem · 2025 · PMID 39806977 · Publisher ↗
INTRODUCTION: Epilepsy encompasses numerous syndromes characterized by spontaneous, intermittent, and abnormal electrical activity in the brain. Affecting about 1-2% of the population, it is estimated that approximately...
INTRODUCTION: Epilepsy encompasses numerous syndromes characterized by spontaneous, intermittent, and abnormal electrical activity in the brain. Affecting about 1-2% of the population, it is estimated that approximately 30-40% of patients experience refractory epilepsy, which does not respond to traditional anticonvulsant drugs. METHODS: Therefore, developing novel, safe, and effective antiepileptic drugs remains a medical need. In this study, we synthesized a series of isoindoline-1,3-dione derivatives and evaluated their anticonvulsant effects. RESULTS: Compounds (2a-j) and (5) were obtained with yields ranging from 52-97%. These compounds were assessed for their protective effects on the following parameters: a) time to first seizure (seizure latency), b) seizure duration, and c) mortality rate post-seizure. The most active compound, (2a), increased seizure latency, reduced seizure duration, and lowered the mortality rate. CONCLUSION: These findings indicate that compound (2a) is a promising new anticonvulsant prototype, offering an alternative to current anticonvulsant drugs.
Recent Developments in Azetidinone-Azole Conjugates: Emerging Antimicrobial Potentials.
Mehta DK, Chaurasiya R, Das R
Med Chem · 2025 · PMID 39791182 · Publisher ↗
The emergence of multidrug-resistant microbial strains poses a significant challenge to global public health. In response, researchers have been exploring innovative antimicrobial agents with enhanced efficacy and novel...
The emergence of multidrug-resistant microbial strains poses a significant challenge to global public health. In response, researchers have been exploring innovative antimicrobial agents with enhanced efficacy and novel mechanisms of action. One promising approach involves the synthesis of hybrid molecules combining azetidinone and azole moieties, capitalizing on the respective antimicrobial properties of both structural elements. Natural and synthetic azetidinone derivatives hold a prominent position among medicinally significant compounds due to their varied and potent antibiotic activities. Interest persists in discovering new synthetic methods and refining existing ones, as well as applying these methods to create novel, biologically active azetidinone derivatives. Additionally, azoles are highly regarded in pharmaceuticals for their broad efficacy, tolerability, and oral availability. By merging these two pharmacophores, researchers aim to create compounds with synergistic or additive antimicrobial effects, potentially overcoming existing resistance mechanisms. Various synthetic strategies, including click chemistry and multicomponent reactions, have been employed to prepare these hybrid molecules efficiently. The antimicrobial potential of azetidinone-azole conjugates has been extensively evaluated against a spectrum of pathogens, including bacteria, fungi, and protozoa. These studies have demonstrated promising results, with several compounds exhibiting potent activity against both Gram-positive and Gramnegative bacteria, as well as clinically relevant fungal strains. Furthermore, SAR studies have provided valuable insights into the key structural features governing the antimicrobial properties of these conjugates, facilitating further optimization and rational design. In conclusion, the development of azetidinone-azole hybrids represents a promising avenue in the quest for novel antimicrobial agents. This study presents a comprehensive overview of recent advancements in synthesis and antimicrobial evaluation of azetidinone-azole conjugates.
Marine-Derived Compound Targeting mTOR and FGFR-2: A Promising Strategy for Breast, Lung, and Colorectal Cancer Therapy.
Mythili VMR, Kumaran K, Chattopadhyay S … +6 more , Basha SA, Sekar S, Senthil S, Prabhu D, Rangasamy K, ArulJothi KN
Med Chem · 2025 · PMID 39781734 · Publisher ↗
INTRODUCTION: The marine habitat is a plentiful source of diverse, active compounds that are extensively utilised for their medicinal properties. Pharmaceutical trends have currently changed towards utilising a diverse r...
INTRODUCTION: The marine habitat is a plentiful source of diverse, active compounds that are extensively utilised for their medicinal properties. Pharmaceutical trends have currently changed towards utilising a diverse range of goods derived from the marine environment. METHODS: This study aimed to examine the inhibitory effects of bioactive chemicals derived from marine algae and bacteria. The identification of these compounds was carried out through the process of Gas Chromatography-Mass Spectrometry (GC-MS) profiling. Subsequently, these compounds were subjected to docking simulations against a specific set of target proteins that are known to be frequently overexpressed in three distinct types of cancer. RESULTS: From the docking results, the ligand 1,4:3,6:5,7-Tribenzal-beta-mannoheptitol was found to be effective against the proteins mTOR (PDB ID: 4JSV) and FGFR2 (PDB ID:6V6Q). The findings of molecular simulation highlight that the investigated compound gets integrated with the target proteins effectively. CONCLUSION: These marine derived compounds hold significant potential for further development and exploration in the field of cancer therapeutics.
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