Current topics in medicinal chemistry最新文献

{"title":"Synthesis, Structure-Activity Studies, and Therapeutic Potential of Met-enkephalin Derivatives.","authors":"Krystyna Dzierzbicka, Monika Gensicka-Kowalewska","doi":"10.2174/0115680266485871260827072414","DOIUrl":"https://doi.org/10.2174/0115680266485871260827072414","url":null,"abstract":"<p><p>One potential drug with analgesic, anticancer, and immune-enhancing properties is the endogenous pentapeptide M-ENK (opioid growth factor, OGF). A significant problem limiting its therapeutic application is its low bioavailability and short half-life in human plasma. Therefore, new analogues, as well as suitable delivery vehicles and administration routes for these potential drugs, are being sought. This article reviews the synthesis methods for OGF and its analogues, as well as the structure-activity relationships. Among other things, it describes: Compounds obtained by shortening or modifying the amino acid sequence in the peptide chain, methylated derivatives, compounds with hydrazine and phenylhydrazine, and with quercetin and resveratrol, which exhibit antioxidant properties, as well as derivatives containing bifunctional adamantane analogs, glycosylated derivatives with increased bioavailability, derivatives containing trifluoromethylamino acid residues in the G2 or G3 position, alkylamide derivatives, cyclic analogs containing thiazoles, cyclic peptidomimetic analogs, and the OGF-Gem conjugate. The M-ENK nanocarrier with RGD molecules is also presented for the controlled delivery of OGF to cancer cells. We highlight OGF and its derivatives in anticancer, analgesic, and immunomodulatory studies, and the potential for use in the treatment of other diseases, such as neurodegenerative (Alzheimer's, Parkinson's), diabetes, and viral diseases. The therapeutic potential of OGF is very large; therefore, it can be expected that the synthesis of new analogues and conjugates with used chemotherapeutic agents will be continued.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial and Antibiofilm Properties of (E,E)-Farnesol Diamine-Derivatives: Potential New Agents Against Methicillin-Resistant Staphylococcus aureus and Escherichia coli.","authors":"Tainara Aparecida Nunes Ribeiro, Grazielle Aparecida Dos Santos, Thainá Elizabeth Freitas, Gabriel Dos Santos E Silva, Dijovani Batista Dos Reis, Fábio Aguiar-Alves, Marcus Vinicius Nora de Souza, Daniel Crístian Ferreira Soares, Mauricio Frota Saraiva, Daniela Sachs","doi":"10.2174/0115680266461065260522113229","DOIUrl":"https://doi.org/10.2174/0115680266461065260522113229","url":null,"abstract":"<p><strong>Introduction: </strong>Antimicrobial resistance, particularly when associated with biofilm formation, represents a major global health challenge. In this context, this study aimed to design, synthesize, and evaluate the in vitro biological activity of (E,E)-farnesylethane-1,2-diamine (4a) and (E,E)-farnesylpiperazine (4b), as dihydrochloride salts.</p><p><strong>Methodology: </strong>The compounds were synthesized following literature protocols. Their antibacterial activity was evaluated by determining Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against Staphylococcus aureus (ATCC 25923), methicillinresistant S. aureus (HU25), and Escherichia coli (ATCC 25922). Biofilm formation was evaluated under subinhibitory conditions by quantifying biomass and viable cells. Experiments were conducted in triplicate and analyzed statistically. Biofilm morphology was examined using Scanning Electron Microscopy (SEM).</p><p><strong>Results: </strong>(E,E)-Farnesol exhibited activity against Gram-positive strains (MIC 64 μg/mL for ATCC 25923 and 32 μg/mL for HU25), with no bactericidal effect (MBC >512 μg/mL), indicating a bacteriostatic profile. In contrast, derivatives 4a and 4b displayed bactericidal activity against both Gram-positive and Gram-negative strains (MIC/MBC 32-64 μg/mL; MBC/MIC = 1). In biofilm assays, compound 4b reduced viable cell counts by over 90% across all strains (P < 0.001), while 4a showed moderate inhibition. SEM analysis confirmed reduced biofilm density and morphological alterations, particularly in Gram-positive bacteria.</p><p><strong>Discussion: </strong>Structural modification of (E,E)-farnesol significantly enhanced antibacterial and antibiofilm activity. Its derivatives demonstrate therapeutic potential against multidrug-resistant bacteria. Limitations include restriction to in vitro assays; further in vivo and cytotoxicity studies are needed.</p><p><strong>Conclusion: </strong>Compounds 4a and 4b emerge as promising candidates for further development, although additional in vivo and toxicity studies are required.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Flavonol Glucoside from Turpinia montana Kurz and Its Synergistic NO Inhibitory Activity with a Triterpene Glucoside.","authors":"Le Thanh Huong, Vu Mai Thao, Nguyen Xuan Nhiem, Nguyen Hai Dang","doi":"10.2174/0115680266478384260819050658","DOIUrl":"https://doi.org/10.2174/0115680266478384260819050658","url":null,"abstract":"<p><strong>Introduction: </strong>The purpose of this study was to analyze the anti-inflammatory potential of the phytochemical constituents of Turpinia montana Kurz, with a focus on nitric oxide (NO) inhibition and potential synergistic effects among isolated substances.</p><p><strong>Methods: </strong>The chemicals were isolated from methanolic extracts of T. montana leaves and twigs using combined chromatographic methods. The ability of each compound to decrease NO generation in RAW 264.7 macrophages activated with LPS was examined. Combination tests were used to further evaluate synergistic interactions, and the Chou-Talalay method was used for quantitative analysis.</p><p><strong>Results: </strong>One new flavonol glucoside, 7-O-(1,1-dimethyl-3-oxobutan-1-y1)kaempferol 3-O-β-Dglucopyranoside (1) and seven known compounds, kaempferol 3-O-β-D-glucopyranoside (2), 2α,3β,19α-trihydroxy-5α,9α-urs-12-en-28-oic acid-28-O-β-D-glucopyranosyl ester (3), pedunculoside (4), rotungenoside (5), quadranoside III (6), urolic acid (7), and icariside E3 (8) were isolated. Moderate NO inhibitory activity was demonstrated by compounds 1, 3, and 4. Increased effects were found in combination experiments, especially for the combination Comp.1/Comp. 4, which showed consistent synergy with DRI values of roughly 4-9.</p><p><strong>Discussion: </strong>The anti-inflammatory properties of T. montana may result from the consequence of synergistic interactions between its ingredients. It may reflect the value of combination-based phytochemical approaches.</p><p><strong>Conclusion: </strong>The study confirms the anti-inflammatory properties of T. montana leaves and twigs. The overall bioactivity may be partially attributable to synergistic interactions.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanochitosan as a Multifunctional Platform for HIV Prevention and Therapy: From Mucosal Defense to Targeted Drug Delivery and Mathematical Modeling.","authors":"Hussein Nemati, Seyed Morteza Naghib, Ghasem Takdehghan","doi":"10.2174/0115680266451676260817091340","DOIUrl":"https://doi.org/10.2174/0115680266451676260817091340","url":null,"abstract":"<p><p>Despite significant progress in the global fight against HIV/AIDS, the disease is still a serious public health problem around the globe. Current ARV therapy (ART) has transformed HIV into a chronic illness from a death sentence; however, limitations such as low drug bioavailability, off-target toxicity, resistant strain development, and the presence of latent viral reservoirs are still major hurdles to elimination. In the last few years, nanochitosan (NCH) has gained increasing attention as a multifunctional and biocompatible nanomaterial with the promise of fulfilling these unmet clinical demands. Its inherent properties of mucoadhesion, antimicrobial activity, biodegradability, and immunomodulation place NCH in the most suitable position as a prospective agent for HIV prevention and treatment. NCH could serve as a carrier for directed and controlled delivery of antiretroviral (ARV) agents, enhance residence time at mucosal sites, and increase penetration through biological barriers to augment therapeutic effectiveness and minimize systemic toxicity. Its cationic properties also allow direct interaction with the viral envelope's negative charge, potentially inhibiting viral entry and replication. This review critically examines recent advances in NCH-based approaches, including prophylactic products such as intravaginal gels and films, targeted ART delivery systems for latent reservoirs, and new insights into NCH's direct antiviral activity. Lastly, the potential role of mathematical modeling in predicting viral load behavior and in justifying dosing regimens quantitatively is debated. Translational hurdles of paramount concern, e.g., large-scale production, long-term safety, regulatory approval, and cost-effectiveness, are also addressed. By uniting nanotechnology, virology, and systems pharmacology, this article positions NCH as a next-generation platform capable of revolutionizing HIV prevention and treatment worldwide.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Herbal Nanomedicine for Cardiovascular Therapeutics.","authors":"Mohammad Mujahid","doi":"10.2174/0115680266413983251128111127","DOIUrl":"https://doi.org/10.2174/0115680266413983251128111127","url":null,"abstract":"<p><p>Cardiovascular Diseases (CVDs) are still the leading cause of illness and death worldwide, even though there have been improvements in traditional treatments. Current therapies, such as medications and surgeries, often have limitations like side effects, high costs, and inconsistent effectiveness. Herbal medicine has a long history of use in traditional systems and offers a wide range of natural compounds that may protect the heart. However, there are challenges in using herbal medicine clinically, including poor absorption in the body, instability of active ingredients, and inability to target specific areas. A new approach called herbal nanopharmacology combines the benefits of herbal medicine with nanotechnology to overcome these obstacles. This field is still relatively unexplored, especially regarding specific CVDs. The important aspects cover the epidemiology and pathophysiology of CVDs, herbs and their therapies, alongside the most recent advances in medicine. Specific conditions such as hypertension, atherosclerosis, and myocardial infarction are further examined in terms of the application of herbal nanopharmacology, with supporting preclinical and clinical evaluation with safety assessment. This article discusses the need for additional research and development of hybrid medicine, combining nanobiotechnology and herbal medicine, to treat conditions such as CVDs. This review aims to reduce the burden by collating salient points from various studies on herbal nanopharmacology and bioactive compounds for the prevention and treatment of CVDs. It assimilates work in the field on bioactive constituents, their modes of action, and principles of nanotechnology in medicine.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Autoimmunity in Type 1 Diabetes: Emerging Immunomodulatory Therapies.","authors":"Jasvinder Saini, Dushyant, Jagdeep Singh, Ashwani K Dhingra, Shabnam Khan, Smita Narwal, Neha Yadav","doi":"10.2174/0115680266429809260723195012","DOIUrl":"https://doi.org/10.2174/0115680266429809260723195012","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) continues to be a complex, multifactorial autoimmune condition characterized by targeted destruction of pancreatic β-cells and permanent insulin dependence. How tremendous the change has been since the advent of insulin therapy, yet T1D patients remain at catastrophic risk from acute complications and chronic vascular injury, calling for more potent disease-modifying therapies. Developments in immunology and genetics have unraveled the interaction of environmental trigger events, including viral infection and gut microbiota, with genetic susceptibility, i.e., HLA class II alleles, on the aberration of immune tolerance and induction of β- cell autoimmunity. The last few decades have seen remarkable advances in the pathogenesis of T1D, including the discovery of β-cell autoantibodies and the pivotal role of autoreactive T cells. However, therapeutic trials in humans of immunomodulatory interventions, such as cyclosporine, anti-CD3 antibodies, and tolerogenic dendritic cells, have, to date, shown only temporary preservation of native insulin secretion, with safety limitations or failure to sustain efficacy being significant limitation. In parallel, efforts at inducing antigen-specific tolerance and microbiota modification have been promising in preclinical models but are still to be validated in humans. Technological advances, including continuous glucose monitoring and artificial pancreas systems, have enhanced glycemic management and quality of life without influencing causative autoimmunity. New strategies, β-cell replacement by transplant or xenograft, genetic engineering to favor immune evasion, and gene therapy for insulin production promise more definitive cures, but much remains in the path of safety, immune rejection, and long-term efficacy. Finally, in the years to come, the management of T1D will be a blend of early diagnosis, customized immunomodulation, improved sensing of glucose, and regeneration. Research on the genetic, immunologic, and environmental determinants for T1D and the creation of safer and more potent therapies will continue to be needed to advance beyond disease symptomatology management to disease modification and prevention.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferulic Acid and Brain Health: A Defender Against Alzheimer's Disease, Parkinson's Disease, and Neuroinflammation.","authors":"Niraj Kumar Singh, Ghaleb Oriquat, Ishika Jain, Mahima Chaudhary, Yasser Mohsen Khlyl, Navin Kumar Tailor","doi":"10.2174/0115680266493487260611111705","DOIUrl":"https://doi.org/10.2174/0115680266493487260611111705","url":null,"abstract":"<p><p>Neuroinflammation is the body's immune reaction that occurs inside the central nervous system to keep brain cells balanced and healthy. Uncontrolled and chronic neuroinflammation can start damaging neuronal cells and lead to neurodegenerative diseases. Glial cells, especially microglia and astrocytes, play an important role in this process. Microglia act as immune guards of the brain, shifting between protective and harmful states depending on certain signals such as NADPH oxidase 2, histone deacetylases, and transforming growth factor. Astrocytes support neurons and maintain the blood-brain barrier. During injury or stress, they become overactive and release numerous chemicals that make inflammation worse. Further, neuroinflammation is controlled by several signalling pathways, including NF-κB, PI3K/Akt, and MAPK. When these systems lose their balance, they cause ongoing inflammation and oxidative stress, which eventually harm brain cells. During the progression of neurodegenerative disorders, especially Alzheimer's Disease (AD) and Parkinson's Disease (PD), overactive microglia and astrocytes release large amounts of cytokines, reactive oxygen species, and inflammasome components that speed up neuron loss. The constant interaction between NF-κB, NLRP3, and oxidative stress worsens this damage, linking faulty molecular signals with the progression of these disorders. Ferulic acid, a natural antioxidant found in grains, fruits, and vegetables, has shown remarkable protective effects on the brain. It is biologically synthesized from aromatic amino acids L-phenylalanine and L-tyrosine through the shikimate pathway. By clearing free radicals and stopping lipid damage, ferulic acid protects neurons from degeneration. Experimental studies have shown that ferulic acid offers significant antioxidant and anti-neuroinflammatory effects and prevents the accumulation of harmful proteins, such as Aβ and α-synuclein, in the brain. Furthermore, ferulic acid has a strong capacity to modulate several cellular and molecular signaling pathways, including Nrf2/HO-1, NF-κB, and MAPK, which are closely linked to the development and progression of neurodegenerative disorders such as AD and PD. Interestingly, ferulic acid inhibits the generation of pro-inflammatory mediators, ameliorates mitochondrial dysfunction, prevents apoptosis, and consequently protects cholinergic and dopaminergic neurons in the brain, thereby exhibiting remarkable neuroprotective effects. Thus, the current review addressed that ferulic acid is considered a promising natural compound that could be an alternative natural phytoconstituent for the prevention and management of neuroinflammationassociated neurodegenerative disorders like AD and PD.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total Flavonoids from Hawthorn Leaves Alleviate Acute Inflammatory Responses Following Spinal Cord Injury by Downregulating the TLR4/NF-Κb Signaling Pathway.","authors":"Wenwen Fu, Ting Zhu, Gaofeng Zeng, Tenghui Ma","doi":"10.2174/0115680266470070260730104635","DOIUrl":"https://doi.org/10.2174/0115680266470070260730104635","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the anti-inflammatory mechanisms of TFHL in SCI through in vivo and in vitro experiments.</p><p><strong>Methods: </strong>A SCI model was established using Sprague-Dawley rats. TFHL was administered via intraperitoneal injection. Microglial cells were stimulated with lipopolysaccharide (LPS) to induce inflammation, followed by TFHL treatment. Behavioral assessments (BBB scores), histological staining, immunoblotting, and quantitative real-time PCR were performed. These indicators evaluated the effects of TFHL on neuronal survival, inflammatory responses, and associated molecular pathways after SCI.</p><p><strong>Results: </strong>TFHL promoted motor function recovery and preserved residual neurons following SCI. Additionally, it significantly inhibited TLR4 complex formation, suppressed NF-κB nuclear translocation, and reduced IL-1β, IL-6, and TNF-α mRNA expression.</p><p><strong>Discussion: </strong>This study demonstrated for the first time that TFHL inhibits the TLR4/NF-κB pathway to exert anti-inflammatory and neuroprotective effects after SCI, as indicated by decreased microglial activation and pro-inflammatory cytokine levels. Although causal validation (e.g., TLR4 knockdown) was not performed, biochemical data (p-p65, p-IκBα, IκBα) support pathway inhibition. These findings provide pharmacological support for TFHL as a potential therapeutic candidate for SCI.</p><p><strong>Conclusion: </strong>TFHL exerts neuroprotective effects by inhibiting the TLR4/NF-κB pathway, and this mechanism at least partially mediates its beneficial effects in SCI.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Modifiers and Synthetic Lethality in Cancer Therapy: Emerging Targets Beyond Traditional Approaches.","authors":"Venkatesh Kamath, Vasudev Pai, Bhavana Bhat, Chandrasekhar K S, Pawan G Nayak, Aravinda Pai","doi":"10.2174/0115680266453780260728100531","DOIUrl":"https://doi.org/10.2174/0115680266453780260728100531","url":null,"abstract":"<p><p>As the field of anticancer drug development is constantly changing, combining synthetic lethality with epigenetic modifiers opens up new possibilities for targets that fall outside the traditional drug target range. Enzymes involved in DNA methylation and histone modification are examples of epigenetic modifiers that promote gene expression without altering the DNA sequence of the gene. These mechanisms play a key role in carcinogenesis when they are altered, as they downregulate tumor suppressor genes and overexpress oncogenic pathways. Synthetic lethality is a phenomenon in which simultaneous mutations or perturbations of two genes result in cell death, but alterations to one gene alone do not cause cell death. It was first observed in genetic research conducted on model organisms, such as fruit flies and fungi. The most well-known example of this idea from the perspective of cancer treatment is PARP inhibitors, which are effective in tumors with BRCA1/2 mutations, where further failure of DNA repair results in cell sensitization. Building on the concept of synthetic lethality, current research focuses on exploiting epigenetic flaws that are common in cancer cells. For example, when chromatin remodelers or methyltransferases cease to function, malignant cells undergo genetic rewiring, rendering them vulnerable to treatment. Recent research has produced some striking examples of synthetic-lethal drug interactions and biomarkers used in metagenomics for personalized medicine by targeting the secondary pathways used by cancer cells as a result of primary loss-of-function mutations, which selectively kill cancer cells while sparing healthy cells. The discovery of actionable epigenetic dependencies and overcoming tumor heterogeneity remain the largest challenges in translating these fascinating scientific discoveries to the clinic. The convergence of epigenetic modulators with synthetic-lethality-based therapeutic architectures is poised to define a transformative paradigm in precision oncology. By orchestrating multilayered perturbations across chromatin-regulatory networks, DNA damage-response pathways, and context-specific vulnerability nodes, this integrative strategy surpasses the limitations of conventional target-centric pharmacology and enables mechanistically rational, synergistic antitumor interventions.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1-Deazapurine-Based Alpha-Glucosidase Inhibitors: A Computational Approach for the Treatment of Type 2 Diabetes Mellitus.","authors":"Faiza Boukli Hacene, Hocine Allali, Sabri Ahmed Cherrak, Wassila Soufi, Said Ghalem, Salim Bouchentouf, Radosław Kowalski","doi":"10.2174/0115680266475871260724042822","DOIUrl":"https://doi.org/10.2174/0115680266475871260724042822","url":null,"abstract":"<p><strong>Introduction: </strong>Optimal therapeutic control of Type 2 Diabetes (T2D) depends on designing Alpha-Glucosidase Inhibitors (AGIs) with high potency. This study employs a rigorous computational approach to evaluate 1-deazapurine-derived ligands, examining their interaction modes and pharmacochemical attributes.</p><p><strong>Methods: </strong>The methodology involves drug-likeness evaluation, molecular docking, and Molecular Dynamics (MD) simulations to elucidate the thermodynamic stability of the complexes. A key feature is the integration of a detailed Structure-Activity Relationship (SAR) analysis, demonstrating high consistency between computational rankings and established biological inhibitory profiles.</p><p><strong>Results: </strong>The screening revealed that heteroaromatic rings and bulky aromatic moieties were critical structural determinants for potency. Among the screen compounds, 6-(2-hydroxybenzoyl)-3- (2-phenylethyl)imidazo[4,5-b]pyridine-5-methyl carboxylate (L14), 5-(furan-2-yl)-3-(4- methoxybenzyl)-2-phenyl-7-(trifluoromethyl)imidazo[4,5-b]pyridine (L11), and 3-[2- phenylethyl]-5-thiophene-2-yl-7-(trifluoromethyl)imidazo[4,5-b]pyridine (L4) stood out for their optimal binding affinities. In particular, L11 emerged as the most significant candidate due to its superior interaction energy and structural stability, directly reflecting observed biological trends.</p><p><strong>Discussion: </strong>These results, supported by favorable ADMET profiles, provide a robust scientific rationale for these ligands as lead compounds for T2D management. While the computational insights are highly consistent with observed trends, further studies will address any potential limitations before progressing.</p><p><strong>Conclusion: </strong>This study establishes a solid methodological framework for future in vitro and in vivo experimental validation of 1-deazapurine derivatives as potent therapeutic agents.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}