Current Medicinal Chemistry[JOURNAL]
Sun
200 papers
Therapeutic Applications of Ficus deltoidea: An Integrative Review of Its Pharmacological Properties.
Tan CY, Choo YM
Curr Med Chem · 2026 May · PMID 42227524 · Publisher ↗
Ficus deltoidea (FD), an herbal medicine commonly used as a traditional medicine in Southeast Asia, is increasingly attracting scientific interest due to its vast potential benefits. The current review aims to incorporat...
Ficus deltoidea (FD), an herbal medicine commonly used as a traditional medicine in Southeast Asia, is increasingly attracting scientific interest due to its vast potential benefits. The current review aims to incorporate the latest scientific data on its therapeutic potential, which includes its effects in metabolic, cardiovascular, immune, anti-inflammatory, antimicrobial, regenerative, reproductive, and anticancer aspects. Evidence from in vitro and in vivo studies indicates FD's potential mechanisms in managing diseases by modulation of oxidative stress, inflammatory signaling, hormonal regulation, extracellular matrix stabilization, and vascular homeostasis. The current data demonstrated promising results in managing diseases such as metabolic disorders, tissue regeneration, infection control, bone preservation, and reproductive health. Although its reported activities have been demonstrated by its crude extracts, the specific phytoconstituents responsible remain to be completely elucidated. Further studies are warranted to confirm FD's therapeutic efficacy. However, based on current evidence, FD can be regarded as a versatile and multi-functional herbal medicine.
Design, Synthesis, and Pharmacological Characterization of Substituted Quinoxalines as NOP Receptor Ligands.
Kyle DJ, Tsuno N, Tafesse L … +16 more , Ueno T, Yamada T, Shinohara S, Hasebe N, Iso Y, Shan S, Bhargava S, Crumley G, Tanaka N, Yemawaki K, Fuchino K, Knappenberger T, Hummel M, Whiteside GT, Taoda Y, Kato A
Curr Med Chem · 2026 May · PMID 42227523 · Publisher ↗
INTRODUCTION: The goal of this work was the discovery of moderate-efficacy, selective, partial agonists of the nociceptin/orphanin-FQ peptide (NOP) receptor. METHODS: A novel collection of quinoxaline-containing molecule...
INTRODUCTION: The goal of this work was the discovery of moderate-efficacy, selective, partial agonists of the nociceptin/orphanin-FQ peptide (NOP) receptor. METHODS: A novel collection of quinoxaline-containing molecules was designed, synthesized, and assayed against NOP and mu-opioid receptors in vitro to establish the relationship between structural modification and pharmacological activity. The lead molecule identified was further assessed in vivo to determine brain penetration, analgesic effects in rodent models of pain, and motor deficits. RESULTS: This SAR approach revealed that the phenyl portion of the quinoxaline is highly sensitive to modification. The unsubstituted phenyl produced a potent partial agonist (5), whereas most other substitutions created presumed antagonists or molecules that bind poorly to the receptor. Compound 5 was analgesic in rodent models of inflammatory and neuropathic pain at doses that did not produce motor deficits. DISCUSSION: The goal of this work was achieved in discovering moderate-efficacy, selective, partial agonists of the NOP receptor. The analgesic efficacy of compound 5 is consistent with the effects of other NOP agonists in animal pain models. The partial agonist nature of 5 likely imparts a wider preclinical therapeutic index compared to full agonists. CONCLUSION: The discovery of sunobinop (compound 5), a NOP partial agonist highly selective for NOP in vitro, was significant. Compound 5 produced antihyperalgesic efficacy in rodents and has progressed to clinical trials.
Apoptosis, Pyroptosis, and Necroptosis (PANoptosis) may be Present in Renal Ischemic Injury.
Wang L, Lu S, Zhao D … +5 more , Hu G, Tang G, Xiong K, Tang J, Yan W
Curr Med Chem · 2026 May · PMID 42227522 · Publisher ↗
INTRODUCTION: Emerging evidence suggests that a novel inflammatory programmed cell death pathway, PANoptosis-entailing the co-activation of apoptosis, pyroptosis, and necroptosis-may contribute to renal ischemic injury....
INTRODUCTION: Emerging evidence suggests that a novel inflammatory programmed cell death pathway, PANoptosis-entailing the co-activation of apoptosis, pyroptosis, and necroptosis-may contribute to renal ischemic injury. While growing research implicates PANoptosis in the pathogenesis of diverse ischemic conditions, its specific role in AKI has not been thoroughly elucidated. METHODS: To test whether PANoptosis exists in renal ischemia diseases, we screened renal ischemia injury involving apoptosis, pyroptosis, and necroptosis as the research model and analyzed the data. Meanwhile, we detected the expression of several marker proteins (cleaved caspase-3, p-MLKL, NLRP3, and GSDMD) in HK-2 cells following ischemic injury. RESULTS: The bibliometric results indicate that there is a large number of studies on apoptosis, pyroptosis, and necroptosis in cell and animal models simulating renal ischemia-reperfusion injury. Meanwhile, the experimental results show that in the ischemia-reperfusion injury model of HK-2 cells, the expression levels of key molecules involved in apoptosis, pyroptosis, and necroptosis change. DISCUSSION: Our results demonstrate the involvement of PANoptosis in renal ischemic injury, offering a basis for targeted therapies against renal ischemia-related diseases and supporting the development of PANoptosis inhibitors. CONCLUSION: Collectively, our findings indicate that a PANoptosis-like cell death process occurs in renal ischemic injury.
Association of Oral Contraceptives with Adverse Pregnancy Outcomes: A Mendelian Randomization and Colocalization Study.
Liu P, Dang C, Liu J … +2 more , Yu X, Sun Z
Curr Med Chem · 2026 May · PMID 42227521 · Publisher ↗
INTRODUCTION: This study aimed to investigate the causal relationship and biological mechanism between oral contraceptives (OCs) and adverse pregnancy outcomes using Mendelian randomization (MR) methods. METHODS: We cond...
INTRODUCTION: This study aimed to investigate the causal relationship and biological mechanism between oral contraceptives (OCs) and adverse pregnancy outcomes using Mendelian randomization (MR) methods. METHODS: We conducted a drug-target MR analysis, identifying five OC target genes and using "Ever taken oral contraceptive pill" as an additional genetic instrument. Summary- data-based MR (SMR) and inverse-variance-weighted MR (IVW-MR) were applied, followed by sensitivity, colocalization, and preliminary bioinformatic analyses. RESULTS: IVW-MR analysis revealed no causal association between ever taking OCs and eight adverse pregnancy outcomes (e.g., ectopic pregnancy, preeclampsia). SMR showed suggestive links between NR1I2 expression and placental abruption (OR=13.51, P=0.04) and between SRD5A1 expression and preterm premature rupture of membranes (OR=0.90, P=0.03), which were not statistically significant after false discovery rate correction. Colocalization analysis did not support shared causal variants (posterior probabilities <50%). Enrichment analysis implicated steroid hormone metabolism pathways. DISCUSSION: Our findings do not support a causal effect of OCs on most adverse pregnancy outcomes, suggesting prior observational associations may reflect confounding. The suggestive roles of NR1I2 and SRD5A1 warrant further investigation, given their involvement in placental steroid metabolism and barrier function. CONCLUSION: Our drug-target MR analysis found no causal association between OCs use and adverse pregnancy outcomes. However, the role of steroid hormone metabolism pathways involving genes such as NR1I2 and SRD5A1 requires validation in future studies.
Integrative Multi-Omics Analysis of Circulating Biomarkers Reveals Targetable Pathways in Pelvic Organ Prolapse.
Huang Y, Yang X, Chen K … +2 more , Yang Y, Li H
Curr Med Chem · 2026 May · PMID 42227520 · Publisher ↗
INTRODUCTION: This study aims to investigate plasma proteins and metabolites causally linked to Pelvic Organ Prolapse (POP), and explore the molecular mechanisms using a proteo-metabolomic Mendelian Randomization (MR) fr...
INTRODUCTION: This study aims to investigate plasma proteins and metabolites causally linked to Pelvic Organ Prolapse (POP), and explore the molecular mechanisms using a proteo-metabolomic Mendelian Randomization (MR) framework. METHODS: MR was performed to assess causal relationships between genetically predicted plasma proteins and POP risk, utilizing large-scale proteomic GWAS data. Colocalization analysis and replication in independent cohorts were performed to evaluate the robustness of the genetic associations. To explore potential downstream mechanisms, a two-step MR approach was applied to investigate metabolites associated with sTie2. Circulating sTie2 concentrations were measured in clinical plasma samples by ELISA, and plasma metabolic profiles were characterized using untargeted metabolomics in POP patients and matched controls. RESULTS: Of the 2,994 circulating proteins examined, 11 showed evidence of a potential causal relationship with POP after multiple testing correction. Among these, soluble Tie2 (sTie2) emerged as a prominent candidate, with similar effect estimates observed across independent datasets. Elevated circulating sTie2 levels in POP patients were further supported by ELISA measurements. Further two-step MR analysis identified 27 metabolites linked to sTie2, with paraxanthine showing a significant positive association with POP susceptibility. Importantly, untargeted metabolomics revealed paraxanthine-related caffeine metabolism as the most significantly enriched KEGG pathway in POP plasma, providing cross-platform validation of the MR-inferred metabolic axis. DISCUSSION: These findings indicate that POP may be driven by a previously unrecognized sTie2-paraxanthine axis. This mechanistic link suggests that vascular signaling and metabolic regulation jointly contribute to pelvic floor degeneration, providing a broader framework for understanding disease progression. CONCLUSION: The study identifies sTie2 as a potential causal factor for POP and suggests a new metabolic pathway involving paraxanthine, providing insights into POP pathogenesis and new targets for therapeutic intervention.
Non-coding RNA-Mediated Regulation of the cGAS-STING Pathway in Tumor Immunology: A Systematic Review.
Molavand M, Soufiani MA, Valizadeh A … +2 more , Asadi A, Yousefi B
Curr Med Chem · 2026 May · PMID 42220151 · Publisher ↗
INTRODUCTION/OBJECTIVE: The cGAS-STING pathway, a central sensor of cytosolic DNA, coordinates innate immune and anti-tumor responses, and emerging evidence shows non-coding RNAs (miRNAs, circRNAs, lncRNAs) regulate this...
INTRODUCTION/OBJECTIVE: The cGAS-STING pathway, a central sensor of cytosolic DNA, coordinates innate immune and anti-tumor responses, and emerging evidence shows non-coding RNAs (miRNAs, circRNAs, lncRNAs) regulate this axis in the tumor microenvironment. This systematic review evaluates how ncRNAs modulate cGAS-STING and their effects on anti-tumor immunity. METHODS: Following PRISMA, we searched PubMed, EMBASE, Web of Science, and Scopus through August 9, 2025, for in vitro and in vivo studies on ncRNA regulation of cGAS-STING in cancer; eligible studies were selected according to predefined criteria, and data were extracted and qualitatively synthesized. RESULTS: Eighteen eligible studies were identified, reporting diverse and sometimes conflicting findings. Eight studies showed certain ncRNAs enhance anti-tumor immunity via cGAS-STING activation, whereas two reported inhibitions. Three linked activations increased radiosensitivity; three showed suppressions that contributed to drug resistance and poorer outcomes; and two implicated ncRNA-cGAS-STING modulation in treatment toxicities. DISCUSSION: These findings illustrate the context-dependent, dual role of ncRNAs in regulating cGAS-STING; depending on species, molecular targets, and context, ncRNAs can potentiate anti-tumor immunity and improve efficacy or suppress signaling and drive resistance. This complexity highlights ncRNAs as biomarkers and therapeutic targets but underscores the need to clarify mechanisms, define conditions favoring activation versus suppression, and evaluate consequences in preclinical and clinical models. CONCLUSION: ncRNAs regulate the cGAS-STING axis in the tumor microenvironment, affecting immunotherapy efficacy, radiosensitivity, and toxicity; preclinical and clinical validation is needed to translate these findings into therapies.
MFF Promotes Aggressive Phenotypes and Immunosuppression in Lung Adenocarcinoma via Mitochondrial Dysregulation.
Pu XX, Liu BY, Xue YW
Curr Med Chem · 2026 May · PMID 42220150 · Publisher ↗
INTRODUCTION: Lung Adenocarcinoma (LUAD) remains a leading cause of cancer mortality, driving the need for novel prognostic markers and therapeutic targets. Mitochondrial dynamics, particularly fission, have emerged as a...
INTRODUCTION: Lung Adenocarcinoma (LUAD) remains a leading cause of cancer mortality, driving the need for novel prognostic markers and therapeutic targets. Mitochondrial dynamics, particularly fission, have emerged as a crucial regulator of tumor progression. Emerging evidence highlights the interplay between mitochondrial proteins and immune modulation, yet the role of Mitochondrial Fission Factor (MFF) in shaping the tumor immune microenvironment, particularly its involvement in non-canonical immune checkpoints, remains largely unexplored in LUAD. Herein, we investigate the expression and clinical significance of MFF in LUAD, and explore its potential associations with mitochondrial dynamics, metabolic reprogramming, and immune modulation. METHODS: Gene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) LUAD cohort for bioinformatics analysis. Validation at the protein level was performed using Immunohistochemistry (IHC) on a Tissue Microarray (TMA) containing 42 evaluable paired LUAD and adjacent normal tissues. Bioinformatics analyses included differential expression, survival (Kaplan-Meier, Cox regression), Protein-Protein Interaction (PPI) networks, Gene Set Enrichment Analysis (GSEA), and immune infiltration profiling. RESULTS: MFF was significantly overexpressed in LUAD at both transcript and protein levels and correlated with advanced disease stages, male gender, and poor survival. It served as a robust prognostic biomarker even in early-stage and node-negative subgroups. Beyond its expected association with mitochondrial dynamics regulators (DNM1L/DRP1, MFN1), MFF expression strongly correlated with a hyperactive OXPHOS transcriptional program, identifying a distinct metabolic phenotype. MFF high tumors were characterized by a distinctive immune checkpoint landscape, with reduced expression of PD-1 and CTLA-4, but marked upregulation of B7-H3 (CD276), coupled with broad suppression of immune infiltration and the antigen presentation machinery. DISCUSSION: Our findings establish MFF as a multifunctional hub linking mitochondrial plasticity to metabolic adaptation and immune evasion in LUAD. The strong OXPHOS association suggests MFF-high tumors may act as metabolic sinks, creating a nutrient-deprived microenvironment hostile to infiltrating immune cells. The distinct B7-H3-dominant checkpoint profile further defines a non-inflamed "immune desert" phenotype, offering a potential explanation for resistance to conventional PD-1/CTLA-4 blockade. While our data do not establish causation, we propose three testable hypotheses for this immunosuppressive phenotype: metabolic competition, shared upstream regulation (e.g., androgen receptor signaling), and stress-induced checkpoint switching. CONCLUSION: MFF drives LUAD progression by orchestrating mitochondrial plasticity and fostering a metabolically distinct, B7-H3-dominant "cold" tumor microenvironment. This positions MFF as a robust prognostic biomarker and identifies MFF-high patients as a specific subgroup that may resist conventional immunotherapy but could benefit from emerging B7-H3-directed therapies, including antibody-drug conjugates or chimeric antigen receptor (CAR)-T cells. Further functional studies are warranted to distinguish whether MFF actively regulates these processes or serves as a marker of this aggressive tumor niche.
Review Deciphering the Anticancer Efficacy of Bibenzyl Derivatives of Dendrobium Species in Lung Carcinoma.
Khan F, Rab SO, Saeed M … +3 more , Almansour K, Singh A, Pandey P
Curr Med Chem · 2026 May · PMID 42163699 · Publisher ↗
Metastasis of lung carcinoma is a significant contributor to elevated mortality rates. Globally, it is one of the most fatal carcinomas in terms of mortality and incidence. Despite extensive studies, treatment of lung ca...
Metastasis of lung carcinoma is a significant contributor to elevated mortality rates. Globally, it is one of the most fatal carcinomas in terms of mortality and incidence. Despite extensive studies, treatment of lung cancer remains ineffective because of severe side effects and multidrug resistance. Herbal drugs have been documented to augment the effectiveness of conventional therapies, enhance patients' quality of life, and alleviate chemotherapy-related adverse effects. This review describes the therapeutic potential of Dendrobium plants for the management of lung carcinoma. Dendrobium is comprised of polysaccharides, alkaloids, bibenzyl, sesquiterpenes, phenanthrene, polyphenols, and other chemical compounds. Dendrobium exhibits antitumor properties by suppressing tumor cell proliferation and metastasis, facilitating apoptosis and ferroptosis, and enhancing cellular sensitivity to chemotherapeutic agents. Some of the bibenzyls, including erianin and gigantol, displayed inhibitory potential in NSCLC models via targeting the PI3K/AKT and Wnt/β-catenin signaling pathways and inducing apoptosis and ferroptosis. Therefore, a comprehensive examination of dendrobium mechanisms and bibenzyl compounds in relation to lung cancer needs to be explored. This review sought to assess the anti-lung cancer potential of bibenzyl compounds from Dendrobium, which has been less reported. Keywords employed in this literature search were "dendrobium," "bibenzyl," and "lung cancer," using SciFinder, Google Scholar, NCBI, PubMed, and Embase, which encompass articles from 2010 to 2025.
Metformin Reverses Progesterone Resistance in Endometrial Cancer by Targeting the AMPK-FOXO1-CALB2 Pathway.
Hong L, Lin R, Zhang W … +7 more , Jiao J, Wang C, Wu H, Liao Y, Qiu Q, Xie Q, Gu J
Curr Med Chem · 2026 May · PMID 42163698 · Publisher ↗
INTRODUCTION: Progesterone therapy is standard for fertility-preserving endometrial cancer (ECC) patients, but primary and secondary resistance limit its efficacy. Metformin (MET) combined with progesterone shows promise...
INTRODUCTION: Progesterone therapy is standard for fertility-preserving endometrial cancer (ECC) patients, but primary and secondary resistance limit its efficacy. Metformin (MET) combined with progesterone shows promise, yet the synergistic mechanism remains unclear. MATERIALS AND METHODS: In vitro cellular studies and nude mouse xenograft models were used. Cell proliferation, migration, and apoptosis were assessed by CCK8, flow cytometry, Western blot, and immunofluorescence. RNA sequencing and cell transfection verified that Forkhead box protein O1(FOXO1) inhibits ECC cell proliferation by downregulating Calbindin2 (CALB2). Xenograft models confirmed FOXO1's inhibitory role. RESULTS: MET combined with Megestrol acetate (MPA) inhibited the proliferation of ECC cells and induced cell apoptosis, and its effect was stronger than that of a single drug. MET promoted FOXO1 nuclear localization. FOXO1 suppressed ECC cell proliferation and migration in vitro and in vivo. MET inhibited proliferation via FOXO1-dependent CALB2 downregulation. Both MET treatment and CALB2 knockdown caused mitochondrial Ca2+ overload, membrane potential depolarization, and apoptosis, effects that were reversed by FOXO1 knockdown or CALB2 overexpression. DISCUSSION: MET with MPA inhibits proliferation and induces apoptosis in MPA-sensitive and resistant ECC cells. MET facilitates FOXO1 nuclear localization via adenosine monophosphate-activated protein kinase (AMPK) activation and AKT serine/threonine kinase 1 (Akt) inhibition. CALB2 is a key downstream target of nuclear FOXO1. The AMPK-FOXO1-CALB2 axis may represent a novel pathway activated by MET, inhibiting ECC proliferation and MPA resistance. CONCLUSION: The AMPK-FOXO1-CALB2 axis mediates MET-induced mitochondrial dysfunction and apoptosis, providing a mechanistic basis for MET to overcome progesterone resistance in ECC.
Uncovering Common Anti-Inflammatory Targets of DHEA, 5-AED, Progesterone, and Gestobutanoyl.
Antipova A, Grishina E, Fedotcheva T
Curr Med Chem · 2026 May · PMID 42163697 · Publisher ↗
INTRODUCTION: Androstenes and progestogens possess strong anti-inflammatory and immunomodulatory properties, as well as cytostatic and anti-proliferative effects on certain hormone-dependent tumors. While these steroids...
INTRODUCTION: Androstenes and progestogens possess strong anti-inflammatory and immunomodulatory properties, as well as cytostatic and anti-proliferative effects on certain hormone-dependent tumors. While these steroids have distinct nuclear and membrane receptors, their targets may overlap, influencing immune and inflammatory pathways. The binding affinities of these steroids to shared molecular targets remain insufficiently characterized. This study aimed to identify and compare common binding targets of selected androstenes and progestogens relevant to immune regulation and inflammation. METHODS: Molecular docking analyses were performed to evaluate the binding affinities of Dehydroepiandrosterone (DHEA), 5-Androstenediol (5-AED), Progesterone (P4), and Gestobutanoyl (GB) to receptors and proteins involved in immune and inflammatory processes. RESULTS: Docking results revealed several common targets for both androstenes and progestogens, including Interleukin-6 (IL-6), Constitutive Androstane Receptor (CAR), Pregnane X Receptor (PXR), Progesterone Receptor Membrane Component 1 (PGRMC1), Peroxisome Proliferator-Activated Receptor Alpha (PPARα), and Toll-Like Receptor 4 (TLR4), consistent with their known anti-inflammatory activities. Unexpectedly, progestogens also bind to glucose-6-phosphate dehydrogenase (G6PD), a metabolic enzyme previously considered a specific DHEA target. GB did not bind to nuclear progesterone receptors but promoted IL-6 production in Peripheral Blood Mononuclear Cells (PBMCs) while inhibiting macrophage luminol-dependent chemiluminescence. This suggests that the rapid, non-genomic effects are likely mediated by membrane targets of GB such as PGRMC1 and TLR4. DISCUSSION: These findings indicate substantial overlap in the molecular targets of androstenes and progestogens, supporting their shared anti-inflammatory effects. The unique binding profile of GB, including IL-6 upregulation alongside oxidative burst suppression, highlights its potential to modulate immune responses through non-genomic mechanisms. CONCLUSION: Combined use of androstenes and progestogens may provide therapeutic benefits for acute and chronic inflammatory conditions, with possible additive or synergistic effects when used sequentially or simultaneously.
Melatonin in Health and Disease and its Metabolism by the Gut Microbes: Implications for Deuterium Homeostasis?
Seneff S, Nigh G, Kyriakopoulos AM
Curr Med Chem · 2026 May · PMID 42163696 · Publisher ↗
Deuterium (2H), a heavy isotope of protium (1H), is a naturally occurring element with a significant impact on human metabolism. Despite its natural presence, deuterium can impair mitochondrial function by damaging ATPas...
Deuterium (2H), a heavy isotope of protium (1H), is a naturally occurring element with a significant impact on human metabolism. Despite its natural presence, deuterium can impair mitochondrial function by damaging ATPase pumps; consequently, biological organisms have evolved sophisticated strategies to mitigate the risks of deuterium overload and protect mitochondrial integrity. Multiple enzymes have evolved to prefer hydrogen over deuterium in their reactions to protect these pumps. One class of enzymes is the cytochrome P450 (CYP) enzymes, which oxidize many substrates, mainly in the Endoplasmic Reticulum (ER), often producing water as a by-product. Furthermore, hydrogen peroxide (H2O2), produced in the ER by ERO1, can travel via the cytoplasm to the mitochondria, where it is reduced to two molecules of water via glutathione peroxidase. Melatonin is an ancient antioxidant molecule that first appeared in photosynthetic bacteria billions of years ago to protect against oxygen produced by respiration. In this paper, we present a hypothesis that melatonin metabolism in the gut provides deuterium- depleted protons to the enterocyte mitochondria. Few are aware that melatonin, known mainly as the hormone produced by the pineal gland to regulate circadian rhythms, is produced in the gut at 400 times the amount produced by the pineal gland. In the gut lining, melatonin is synthesized from N-acetylserotonin through the addition of a methyl group from S-adenosylmethionine. This methyl group, which we argue is severely deuterium-depleted due to its gut microbial source, is then fully metabolized by CYP2C19 in the ER of enterocytes in the small intestine, producing four molecules of water, which we argue would also be depleted in deuterium. Melatonin is recycled from the gut to the liver multiple times via the bile acids, and it is repeatedly converted back to N-acetylserotonin and regenerated, each time producing four water molecules derived from its methyl group. Butyrate, another nutrient supplied by gut microbes, stimulates the synthesis of serotonin and melatonin from tryptophan in the gut. Melatonin is a powerful antioxidant in mitochondria and promotes a healthy microbiome. Melatonin deficiency is associated with the severity of long COVID, and melatonin supplementation can help minimize side effects.
Network Toxicology and Molecular Docking Reveal the Risk and Potential Mechanisms of VOCs-induced Male Reproductive System Impairment.
Zang Y, Deng C, Sun Y … +3 more , Wei Z, Yang Y, Wang M
Curr Med Chem · 2026 May · PMID 42163695 · Publisher ↗
BACKGROUND: Volatile organic compounds (VOCs) are widely released into the environment through industrial production and daily human activities, posing potential threats to male reproductive health and fertility. This st...
BACKGROUND: Volatile organic compounds (VOCs) are widely released into the environment through industrial production and daily human activities, posing potential threats to male reproductive health and fertility. This study aims to investigate the potential adverse effects of VOCs as atmospheric pollutants on the male reproductive system and to elucidate the underlying molecular mechanisms. METHODS: An integrated approach combining network toxicology, molecular docking, and molecular dynamics (MD) simulations was employed, with prostatitis, erectile dysfunction (ED), epididymitis, and urethritis selected as representative male reproductive diseases. Data from PubChem, ADMETlab 2.0, and SwissADME databases were integrated to screen 17 classes of VOCs and their associated disease-related targets, followed by the identification of core target genes. GO and KEGG pathway enrichment analyses were conducted to elucidate the underlying molecular mechanisms. Molecular docking validation was performed, and MD was conducted on the key protein CASP3. RESULTS: The potential overlapping targets of VOCs with prostatitis, ED, epididymitis, and urethritis were identified as 481, 387, 210, and 182, respectively. Molecular docking and MD results showed that CASP3, ranked as the top core target, exhibited stable binding with VOCs. KEGG pathway analysis indicated that all four diseases were enriched in cancer-related pathways, oxidative stress pathways, and apoptosis-related pathways. DISCUSSION: VOCs bind to key proteins such as CASP3, AKT1, and EGFR, activating signaling pathways including PI3K/Akt, HIF-1α/mTOR, EGFR, and nNOS, thereby disrupting oxidative stress and cellular metabolic disorders, which promote the onset and progression of diseases. CASP3 plays a key role in maintaining the stability of the complex with VOCs through hydrophobic and hydrogen bonding interactions. By interfering with fundamental biological processes, VOCs may induce multi-organ damage in the reproductive system, forming a comorbidity spectrum characterized by inflammation and functional impairment. CONCLUSION: This study demonstrates that VOCs induce male reproductive diseases by binding to key proteins and activating multiple signaling pathways. Monitoring VOC exposure and conducting individual risk assessments hold significant public health implications, while also providing potential therapeutic targets for reproductive diseases.
Chrysin against Endocrine and Reproductive Systems Impairment: Current Evidence and Future Perspectives.
Harifi-Mood MS, Samini F, Farkhondeh T … +1 more , Samarghandian S
Curr Med Chem · 2026 May · PMID 42163694 · Publisher ↗
Endocrine and reproductive disorders are major global health challenges, often associated with by oxidative stress, inflammation, and hormonal imbalances. Conventional treatments can be limited by adverse effects and sub...
Endocrine and reproductive disorders are major global health challenges, often associated with by oxidative stress, inflammation, and hormonal imbalances. Conventional treatments can be limited by adverse effects and suboptimal efficacy, highlighting the need for potentially effective natural compounds with therapeutic potential. Chrysin, a flavonoid found in honey, propolis, and passionflower, exhibits significant antioxidant, anti-inflammatory, and hormone-modulating properties. Preclinical studies indicate that chrysin improves spermatogenesis, testosterone levels, and testicular function in males, supports ovarian health and hormonal regulation in females, and ameliorates dysfunctions of endocrine organs such as the pancreas and thyroid, contributing to enhanced metabolic and hormonal balance. However, its clinical utility is limited by poor solubility, low oral bioavailability, and rapid metabolism. Recent advances in nanoformulations have enhanced its pharmacokinetic profile and therapeutic performance, offering promising strategies for future clinical application. This review summarizes current evidence on chrysin's protective and therapeutic roles in endocrine and reproductive disorders and highlights directions for future translational and clinical research.
Cannabinoids: Therapeutic Applications, Mechanisms, and Challenges in Modern Medicine.
Gasmi A, Noor S, Piscopo S … +1 more , Bjørklund G
Curr Med Chem · 2026 May · PMID 42163693 · Publisher ↗
Cannabinoids are the active compounds of Cannabis sativa, and they are known to be substitutes for meroterpenes. Almost 480 cannabinoids of different types have been discovered, and among them, 110 are known as phytocann...
Cannabinoids are the active compounds of Cannabis sativa, and they are known to be substitutes for meroterpenes. Almost 480 cannabinoids of different types have been discovered, and among them, 110 are known as phytocannabinoids. Several derivatives of cannabinoids are also produced commercially and are used to treat various diseases. Nabilone is a commercially available cannabinoid derivative licensed for use in cancer patients to relieve chemotherapy-induced emesis (CIE). This review aims to provide insight into cannabinoids, their classes, composition, indications, side effects, and related aspects. Delta-9-tetrahydrocannabinol (Δ-9-THC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), and cannabigerovarinic acid (CBGVA) are some of the important components of the cannabis plant. CBD has more advantages because it has non-psychotic effects compared to other cannabinoids. It can act as an effective substance for pain management, treating cancer, stress, and neurological disorders, improving immunity and skin health, and helping treat gastrointestinal disorders. Despite their advantages as therapeutic agents, there are adverse effects linked to the use of cannabinoids. Nausea, dizziness, fatigue, sedation, and anxiety are some of the common side effects. Several in vitro and preclinical studies have been discussed in this review, which validate the effective role of cannabinoids. However, there is a need to perform clinical trials involving human subjects to establish standard formulations, doses, and safety profiles to consider such substances as drugs.
Structure-Based Identification of Natural Product-Derived BCL-2 Inhibitors as Potential Therapeutics for Hepatocellular Carcinoma.
Zoghebi K, Najmi A
Curr Med Chem · 2026 May · PMID 42163692 · Publisher ↗
INTRODUCTION/OBJECTIVE: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, remains a major therapeutic challenge due to its poor prognosis and resistance to conventional therapies. In this stud...
INTRODUCTION/OBJECTIVE: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, remains a major therapeutic challenge due to its poor prognosis and resistance to conventional therapies. In this study, we employed a structure- based virtual screening strategy to identify novel small-molecule inhibitors derived from natural products targeting the anti-apoptotic protein BCL2, a key driver of HCC progression. METHODS: A curated library of 600 phytochemicals was docked against the BCL2 protein model using molecular docking, followed by ADMET profiling and Molecular Dynamics (MD) simulations. RESULTS: Among the screened compounds, three candidates (Azadirone, Hydroxyethylamine scaffold, and Pyridine-3-carboxylic acid) demonstrated strong binding affinity and stable interaction patterns with critical residues such as GLN429 and TRP601. in silico ADMET analysis indicated favorable safety profiles, with no predicted carcinogenicity or toxicity, though oral bioavailability limitations were noted. MD simulations confirmed structural stability and strong protein ligand binding, with Hydroxyethylamine showing the most consistent conformational performance. DISCUSSION: The identified compounds showed potential interactions with the BCL2 target, suggesting the potential of phytochemical-derived molecules as apoptosis-modulating agents in HCC. This combination of docking, ADMET, and MD simulations provided a comprehensive computational evaluation, consistent with the existing trends in natural product-based and AI-aided drug discovery strategies. CONCLUSION: This study presents three lead candidates in natural sources that are likely to be used as BCL2 inhibitors in the treatment of HCC. The integrative computational approach offers an excellent platform for the discovery of apoptosis-targeting therapeutics, hastening their development and facilitating further experimental validation.
An Overview: New Trends in Synthetic Methods and Pharmaceutical Applications of Pyrrole-Derivatives.
Zulu NH, Adeloye AO, Khanye DS
Curr Med Chem · 2026 May · PMID 42152673 · Publisher ↗
Based on the vast applications in biological and therapeutic contexts, heterocyclic compounds, particularly those containing at least one heteroatom like oxygen, sulphur, nitrogen, phosphorus, and selenium, have received...
Based on the vast applications in biological and therapeutic contexts, heterocyclic compounds, particularly those containing at least one heteroatom like oxygen, sulphur, nitrogen, phosphorus, and selenium, have received increased interest in the study of their chemical properties. Apart from their crucial contributions in pharmaceutical applications, their derivatives are recognized to serve such important roles in living systems as found in photosynthesis, oxygen transport, storage, and redox cycling reactions. The goal of this review is to particularly focus on the quantitative reports on new trends in the methods of preparing simple and bulky pyrroles, their various derivatives, including metal complexes and metallacrowns, as well as their potential applications as therapeutics in medicinal chemistry for the treatment of cancer, inflammation, convulsion, diabetes, psychotic, and other chronic diseases.
Computational Insights into Ribavirin's Potential Impact on Major Depressive Disorder: A Network Toxicology Study.
Chen C, Wang T, Fang C … +3 more , Wang X, Shen T, Gao S
Curr Med Chem · 2026 May · PMID 42152672 · Publisher ↗
OBJECTIVE: To elucidate potential molecular intersections between ribavirin and Major Depressive Disorder (MDD) and to generate testable hypotheses regarding neuropsychiatric safety and mechanism of action. METHODS: Riba...
OBJECTIVE: To elucidate potential molecular intersections between ribavirin and Major Depressive Disorder (MDD) and to generate testable hypotheses regarding neuropsychiatric safety and mechanism of action. METHODS: Ribavirin-associated targets were integrated from Swiss Target Prediction, TargetNet, and SuperPred (n = 163), and MDD-related genes were compiled from OMIM and GeneCards (n = 2035). Venn analysis identified 45 overlapping candidates. A STRING-based protein interaction network was analyzed in Cytoscape using CytoNCA to prioritize core targets. Functional interpretation included GO and KEGG enrichment via OmicShare, cell type annotation with PanglaoDB, molecular docking, and transcriptomic cross-validation using the GSE76826 peripheral blood dataset. RESULTS: Five core targets emerged as central nodes, namely CCND1, SIRT1, NFKB1, EP300, and MAPK1, each linked to neurogenesis, synaptic plasticity, immune and inflammatory regulation, epigenetic control, and stress signaling. Enrichment analyses highlighted processes and pathways relevant to MDD, including responses to oxygencontaining compounds, cell death, HIF-1 signaling, neurotrophin signaling, cellular senescence, and ferroptosis. Cell type annotations associated core targets with fibroblasts, dendritic cells, natural killer cells, and neurons. Docking suggested plausible hydrogen- bonded interactions between ribavirin and core proteins. Cross-validation with GSE76826 supported overlap with differentially expressed genes, pathway concordance, and altered expression of select core targets in MDD compared with controls. DISCUSSION: The convergence of targets and pathways with established MDD biology supports the plausibility that ribavirin intersects depression-relevant mechanisms. Limitations include reliance on curated databases, potential hub bias in network topology, limited tissue and cell-type specificity in enrichment, the approximate nature of docking, uncertain brain exposure at clinical doses, and tissue mismatch when using peripheral blood for validation. Clinical attribution is further complicated by co-therapy, underlying infection, and psychosocial factors. These findings are hypothesis-generating and should guide targeted experimental and clinical validation. CONCLUSION: Ribavirin may engage key axes of MDD biology through core targets such as CCND1, SIRT1, NFKB1, EP300, and MAPK1. The results support risk assessment and focused monitoring of depressive symptoms in ribavirin-treated patients and outline priorities for mechanistic validation.
Impact of Intraoperative Coagulation Factor Concentrates during Pediatric Liver Transplantation: A Retrospective, Propensity-Matched Study.
Wang M, Fang F, Hu Y … +5 more , Su D, Kang X, Zhu Z, McQuillan PM, Hu Z
Curr Med Chem · 2026 May · PMID 42152671 · Publisher ↗
INTRODUCTION: Coagulopathy is a common issue in pediatric Liver Transplantation (LT), and bleeding can lead to increased morbidity and mortality. However, there is limited research on the use of coagulation factor comple...
INTRODUCTION: Coagulopathy is a common issue in pediatric Liver Transplantation (LT), and bleeding can lead to increased morbidity and mortality. However, there is limited research on the use of coagulation factor complexes, specifically Fibrinogen Concentrate (FibC) and Prothrombin Complex Concentrate (PCC), in pediatric LT. METHODS: The study identified pediatric patients who underwent LT between March 2019 and December 2024. Patients who received FibC and PCC were categorized into the FibC group (Group F, n=150), while those who did not receive FibC and PCC were assigned to the control group (Group C, n=348). After 1:1 propensity score matching, 118 patients were included in each group for analysis. The primary endpoint was the need for Red Blood Cell (RBC) transfusion in pediatric patients undergoing LT. RESULTS: The volume of RBC infusion during surgery was significantly higher in Group F compared to Group C, with a median [interquartile range] of 800.00 [600.00, 1000.00] ml for Group F versus 600.00 [400.00, 900.00] ml for Group C (p=0.004). During surgery, Group F experienced greater bleeding and required tranexamic acid. Furthermore, 24 hours after surgery, there was no significant difference between the two groups in terms of volume of intraperitoneal drainage or amount of RBC transfusion. The postoperative PT and INR levels in group F were significantly lower than those in group C, whereas fibrinogen levels were significantly elevated. There were no notable differences in postoperative complications, including embolism, between groups. DISCUSSION: The factors affecting the clinical effectiveness of coagulation factor concentrates during pediatric liver transplantation are complex and multifaceted. CONCLUSION: This retrospective study indicated that the use of FibC and PCC as an adjunct to FFP did not lead to decreased transfusion requirements for children experiencing bleeding during liver transplantation. No thromboembolic complications related to FibC and PCC administration were noted.
Vitamin E in Alzheimer's Disease: A Perspective on Antioxidant Therapy.
Bjørklund G, Izmailovich M, Glushkova N … +1 more , Semenova Y
Curr Med Chem · 2026 May · PMID 42152670 · Publisher ↗
This study explores the relationship between vitamin E and Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline, memory loss, and language impairment. Vitamin E is a fat-soluble antio...
This study explores the relationship between vitamin E and Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline, memory loss, and language impairment. Vitamin E is a fat-soluble antioxidant crucial in protecting cells from oxidative damage. The biochemistry and bioavailability of vitamin E are discussed, including its absorption, transport, and storage in the body. The section on interactions between vitamin E and other nutrients and herbals highlights how combining vitamin E supplements with other supplements or medications can affect its absorption, metabolism, and effectiveness. This study also discusses the potential therapeutic effects of vitamin E on AD, including its ability to reduce oxidative stress and inflammation, which are thought to play a role in the pathophysiology of AD. It explores the synergistic effects of vitamin E with pharmaceuticals and potential side effects, and covers the use of vitamin E in combination with other drugs for AD treatment, such as cholinesterase inhibitors and memantine, as well as the possible adverse effects of vitamin E supplementation. Overall, this study highlights the importance of vitamin E in preventing and managing AD and underscores the need for further research in this area.
Circular Circ_0001387 Promotes Hepatocellular Carcinoma Progression via miR-4324/MCM6 Axis and Cell Cycle Pathway Activation.
Zheng X, Yin C
Curr Med Chem · 2026 May · PMID 42152669 · Publisher ↗
INTRODUCTION: Hepatocellular carcinoma (HCC) carries a poor prognosis, and circular RNAs (circRNAs) are pivotal in its biology. This study aimed to investigate the role of a novel circRNA, circ_0001387, in HCC pathophysi...
INTRODUCTION: Hepatocellular carcinoma (HCC) carries a poor prognosis, and circular RNAs (circRNAs) are pivotal in its biology. This study aimed to investigate the role of a novel circRNA, circ_0001387, in HCC pathophysiology. METHODS: A circRNA-miRNA-mRNA axis was identified via bioinformatics analysis of GEO databases. Functional assays included qRT-PCR, CCK-8, wound healing, transwell, flow cytometry for apoptosis/cell cycle, and western blot for protein detection (CDK4, c-Myc, CyclinD1, GSK-3β, p-GSK-3β, E-cadherin, N-cadherin, MCM6). in vivo tumor growth was assessed in nude mouse xenografts. Interactions were validated by dual-luciferase reporter assays. RESULTS: Circ_0001387 and MCM6 were upregulated in HCC tissues and cells, while miR-4324 was downregulated. Overexpression of circ_0001387 promoted HCC cell proliferation, migration, invasion, and tumor growth in vivo, while inhibiting apoptosis and cell cycle arrest. Knockdown produced opposite effects. Mechanistically, circ_0001387 directly sponged miR-4324, which targeted MCM6. Rescue experiments confirmed that miR-4324 inhibition or MCM6 overexpression reversed the effects of circ_0001387 knockdown, whereas MCM6 silencing offset miR-4324 knockdown. DISCUSSION: Our findings delineate a novel oncogenic axis in which circ_0001387 drives HCC progression by sequestering miR-4324 to elevate MCM6 expression. This pathway underscores the significant regulatory role of circRNAs in HCC and aligns with emerging evidence of competing endogenous RNA networks in cancer. Study limitations include the need for further clinical validation of this axis as a biomarker. CONCLUSION: Circ_0001387 facilitates HCC progression via the miR-4324/MCM6 axis, highlighting its potential as a therapeutic target for HCC intervention.
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