Future medicinal chemistry最新文献_第4页

Designing organometallic complexes to induce immunogenic cell death. 设计有机金属配合物诱导免疫原性细胞死亡。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-05 DOI: 10.1080/17568919.2026.2714019

Thomas Scattolin

引用次数: 0

Asymmetric benzazole derivatives as dual antibiofilm and anti-wall teichoic acid agents against Staphylococcus aureus. 不对称苯并唑衍生物作为抗金黄色葡萄球菌的双抗生物膜和抗壁磷壁酸剂。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-10 DOI: 10.1080/17568919.2026.2714028

Mine Buga Aktekin, Zehra Oksuz, Mehmet Abdullah Alagoz, Bahar Uluca Han, Oztekin Algul

{"title":"Asymmetric benzazole derivatives as dual antibiofilm and anti-wall teichoic acid agents against Staphylococcus aureus.","authors":"Mine Buga Aktekin, Zehra Oksuz, Mehmet Abdullah Alagoz, Bahar Uluca Han, Oztekin Algul","doi":"10.1080/17568919.2026.2714028","DOIUrl":"10.1080/17568919.2026.2714028","url":null,"abstract":"Aims: Antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), have renewed interest in antivirulence strategies. This study aimed to design, synthesize, and evaluate asymmetric di‑heterocyclic benzazole derivatives as antibiofilm agents targeting wall teichoic acid (WTA) biosynthesis.Materials and methods: Twenty‑one novel bis‑heterocyclic benzazole derivatives bearing an ethyl‑thio linker were synthesized and characterized. Antibacterial activity was determined by broth microdilution. Antibiofilm activity (inhibition and eradication) was assessed at sub‑minimal inhibitory concentrations (sub‑MICs) using crystal violet. Molecular docking and 200 ns molecular dynamics (MD) simulations were performed against key WTA enzymes (TarGH, TarS, TarM, TarL, and TarJ).Results: Compounds 18, 21, 23, and 24 showed potent antibacterial activity against methicillin‑susceptible S. aureus (MSSA) and MRSA, with MIC values as low as 15.62 µg/mL. All selected compounds significantly inhibited biofilm at sub‑MIC levels. Compound 24 was most effective, with an MBIC50 of 3.90 µg/mL against MSSA and eradicated pre‑formed biofilms at 7.81 µg/mL. Docking and MD simulations revealed stable interactions of compounds 23 and 24 with TarGH and TarS, suggesting a WTA‑targeting mechanism.Conclusions: Di‑heterocyclic benzazole derivatives, especially compound 24, are promising scaffolds for antibiofilm agents against S. aureus. Our findings support further mechanistic and preclinical evaluation as potential antivirulence therapeutics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2337-2355"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701115","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}

引用次数: 0

Synthesis of polyhydroquinoline derivatives as potent antidiabetic and antioxidant agents: in vitro biological activities and computational studies. 作为有效抗糖尿病和抗氧化剂的聚对苯二酚衍生物的合成：体外生物活性和计算研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-15 DOI: 10.1080/17568919.2026.2718768

Sultan Muhammad, Abdul Latif, Aftab Alam, Mumtaz Ali, Ahmed A Elhenawy, Manzoor Ahmad, Shujaat Ahmad, Syed Adnan Ali Shah, Syahrul Imran, Farman Ali Khan

{"title":"Synthesis of polyhydroquinoline derivatives as potent antidiabetic and antioxidant agents: in vitro biological activities and computational studies.","authors":"Sultan Muhammad, Abdul Latif, Aftab Alam, Mumtaz Ali, Ahmed A Elhenawy, Manzoor Ahmad, Shujaat Ahmad, Syed Adnan Ali Shah, Syahrul Imran, Farman Ali Khan","doi":"10.1080/17568919.2026.2718768","DOIUrl":"10.1080/17568919.2026.2718768","url":null,"abstract":"Aims: Diabetes mellitus (DM) is a severe metabolic disease characterized by increased blood glucose levels due to reduced insulin action or secretion. This study aimed to synthesize new polyhydroquinoline (PHQ)-based acyl hydrazide derivatives and assess their potential as dual inhibitors of α-amylase and α-glucosidase enzymes.Materials and methods: Various acyl hydrazide derivatives of PHQ were synthesized via a multi-step reaction and structurally deduced through modern spectroscopic techniques. These compounds were evaluated for their in vitro studies, while molecular docking was performed to gain mechanistic insights into their biological activities.Results and discussion: In the series, compound (2c) emerged as the most potent inhibitor against both enzymes (IC50 = 0.44 ± 0.07 µM and 0.17 ± 0.01 µM, respectively), showing greater efficacy than acarbose. Density functional theory (DFT) analysis revealed valuable insights into the electronic properties and showed the best correlation with the biological targets. Moreover, molecular docking analysis showed good binding interactions with the active sites of both enzymes, which was supported by the experimental activities.Conclusion: These integrated experimental and computational results demonstrate that the polyhydroquinoline scaffold represents a promising platform for developing next-generation antidiabetic therapeutics with enhanced efficacy and favorable safety profiles.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2523-2544"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764086","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}

引用次数: 0

Novel thioether and thioester-based derivatives as promising antibacterial agents with antioxidant potential: design, synthesis, and in silico studies. 新型硫醚和硫酯基衍生物作为具有抗氧化潜力的有前途的抗菌剂：设计，合成和硅研究。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-11 DOI: 10.1080/17568919.2026.2714020

Aya H Othman, Menna M A Abd El-Mageed, Faten Farouk, Ayman B Farag, Safinaz E-S Abbas

{"title":"Novel thioether and thioester-based derivatives as promising antibacterial agents with antioxidant potential: design, synthesis, and in silico studies.","authors":"Aya H Othman, Menna M A Abd El-Mageed, Faten Farouk, Ayman B Farag, Safinaz E-S Abbas","doi":"10.1080/17568919.2026.2714020","DOIUrl":"10.1080/17568919.2026.2714020","url":null,"abstract":"Aim: Development of novel thioethers (5a-g), thioesters (6a-g), and bis-thioethers (8a-h) with antibacterial potential.Materials and methods: Twenty-one novel compounds were synthesized and evaluated for antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. Compounds with significant antibacterial activity were estimated for antioxidant potential and in silico studies.Results and discussion: Eight of the tested compounds demonstrated significant antibacterial activity, particularly versus B. cereus and S. aureus. The minimum inhibitory concentration (MIC) revealed the remarkable antibacterial activity and bactericidal behavior, as demonstrated by minimum bactericidal concentration (MBC) determination and time-kill kinetics studies of 8g and 8h, against S. aureus. Moreover, both compounds exhibited notable antibiofilm activity against S.aureus. Selectivity of the tested compounds as antibacterial agents was confirmed by low cytotoxicity toward normal cells. Remarkably, compounds 8b and 8g exhibited antioxidant potential (ABTS and DPPH) assays in comparison to ascorbic acid. Evaluation of antioxidant markers revealed that 8g displayed an increase in superoxide dismutase (SOD) and malondialdehyde (MDA) level. In silico studies revealed that the compounds exhibited acceptable ADME properties, with strong binding to the bacterial dihydrofolate reductase active site, along with dynamic stability of the DHFR-8g complex.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2301-2318"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design and development of 2,7-disubstituted 6-methoxyquinazolin-4 (3H)-ones as potential anti-cancer agents possibly through downregulation of Wnt/β-catenin/TCF4 signaling pathway. 2,7-二取代6-甲氧基喹唑啉-4 (3H)- 1可能通过下调Wnt/β-catenin/TCF4信号通路而成为潜在的抗癌药物。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-17 DOI: 10.1080/17568919.2026.2714576

Prashant R Murumkar, Kaushik Neogi, Premlal Meher, Rasana Yadav, Karan Joshi, Omkumar Prajapati, Priyanshu Sharma, Poonam Yadav, Devarajan Karunagaran, Prasanta Kumar Nayak, Mange Ram Yadav

{"title":"Design and development of 2,7-disubstituted 6-methoxyquinazolin-4 (3H)-ones as potential anti-cancer agents possibly through downregulation of Wnt/β-catenin/TCF4 signaling pathway.","authors":"Prashant R Murumkar, Kaushik Neogi, Premlal Meher, Rasana Yadav, Karan Joshi, Omkumar Prajapati, Priyanshu Sharma, Poonam Yadav, Devarajan Karunagaran, Prasanta Kumar Nayak, Mange Ram Yadav","doi":"10.1080/17568919.2026.2714576","DOIUrl":"10.1080/17568919.2026.2714576","url":null,"abstract":"Aim: A novel series of 2,7-disubstituted 6-methoxyquinazolin-4(3H)-one derivatives were designed, synthesized, and evaluated for in-vitro anti-cancer potential.Methods: Compounds were docked, synthesiazed and then evaluated for in vitro anti-cancer activity using the sulforhodamine B assay in HCT116 and HepG2 cells. Apoptosis induction was analyzed via morphological changes, Hoechst 33342, and Annexin V/PI staining. The effect on β-catenin/TCF‑mediated transcriptional activity was assessed by TOPFlash/FOPFlash assay, TCF4 and β-catenin protein expression by immunocytofluorescence, and Wnt target genes (like c-MYC and Cyclin D1) mRNA levels by RT-PCR against HCT116 cells. Furthermore, In vitro anti-cancer potential was evaluated against primary human gallbladder cancer cells.Results: The derivatives showed favorable binding with the active site residues on β-catenin and have the potential to disrupt the β-catenin/TCF4 interaction. Most of them have comparable anti-cancer activity to imatinib mesylate. Compound 42D, one of the potent compounds (IC50: 3.89 μM in HCT116; 8.28 μM in HepG2), induced apoptosis, and significantly downregulated β-catenin/TCF4 signaling and downstream targets (c-Myc, Cyclin D1) in HCT116 cells and this could be one of the mechanisms by which it exerts its anti-cancer activity. It showed anti-cancer activity in primary gallbladder cancer cells (IC50: 7.26 μM).Conclusion: Compound (42D) represents a promising molecule as an anti-cancer agent against colon, hepatocellular, and gallbladder cancers targeting the Wnt/β-catenin/TCF4 signaling pathway.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2285-2299"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758487","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}

引用次数: 0

In silico and in vitro evaluation of new sulfonamide derivatives as VEGFR-2 inhibitors for cancer therapy. 新的磺胺衍生物作为VEGFR-2抑制剂用于癌症治疗的硅和体外评价。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-25 DOI: 10.1080/17568919.2026.2718764

Ahmed Wheed Radhi, Hayder Ghanim Chfat, Zahraa Sabbar Omarn, Hayder Kadhim Abbas, Ali Jabbar Radhi, Ehab K Obaid

{"title":"In silico and in vitro evaluation of new sulfonamide derivatives as VEGFR-2 inhibitors for cancer therapy.","authors":"Ahmed Wheed Radhi, Hayder Ghanim Chfat, Zahraa Sabbar Omarn, Hayder Kadhim Abbas, Ali Jabbar Radhi, Ehab K Obaid","doi":"10.1080/17568919.2026.2718764","DOIUrl":"10.1080/17568919.2026.2718764","url":null,"abstract":"Vascular endothelial growth factor receptor 2 (VEGFR-2) is a principal regulator of tumor progression and angiogenesis, which makes it an attractive target for developing and creating anticancer agents. A series of sulfonamide-derived compounds (K1-K5) were designed and evaluated for their ability to inhibit VEGFR-2 and for their cytotoxic activity against HCT-116 (colon), HepG-2 (liver), MCF-7 (breast) human cancer cells, and WI-38 (normal) fibroblasts. All of the compounds produced significant inhibition of VEGFR-2, with IC50values ranging from 0.0917 ± 0.028 µM (K5) to 1.2007 ± 0.013 µM (K1), relative to Sorafenib (IC50 = 0.0525 ± 0.017 µM). The most promising compound was K4, which produced potent inhibition of VEGFR-2 (IC50 = 0.1717 ± 0.027) and the highest selectivity index (SI) of all tested compounds: 25.6 (HCT-116), 14.8 (HepG-2), and 17.0 (MCF-7). In contrast to Sorafenib, whose Selectivity Index (SI) values range between 2.1 and 4.9, the SI values of both Vinblastine and Doxorubicin are less than 2.0 across these particular cell lines. This suggests that K4 has 12 times greater selectivity than Sorafenib and over 25 times greater selectivity than traditional chemotherapeutics. The increased selectivity of K4 can be attributed to the incorporation of a urea-linked sulfonamide moiety, which allows for the formation of hydrogen bonds and minimizes nonspecific hydrophobic interactions. Collectively, these data will demonstrate the importance of designing sulfonamide analogues with optimal structural characteristics to identify effective and specific VEGFR-2 inhibitors and that K4 represents a potentially important candidate for continued preclinical development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2357-2371"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812282","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}

引用次数: 0

Chromanone and chromone scaffolds in cancer and metabolic disorders: advances in synthesis, SAR, and developability (2020-2026). 癌症和代谢性疾病中的铬酮和铬酮支架：合成、SAR和可发展性的进展（2020-2026）。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-19 DOI: 10.1080/17568919.2026.2718762

Manisha Nidhar, Muhammad Afzal, Gaurav Gupta, Surya Nath Pandey, Vaishali Goel, Avijit Mazumder, Pavan Goud, Sachin Kumar Singh, Keshav Raj Paudel, Kamal Dua

{"title":"Chromanone and chromone scaffolds in cancer and metabolic disorders: advances in synthesis, SAR, and developability (2020-2026).","authors":"Manisha Nidhar, Muhammad Afzal, Gaurav Gupta, Surya Nath Pandey, Vaishali Goel, Avijit Mazumder, Pavan Goud, Sachin Kumar Singh, Keshav Raj Paudel, Kamal Dua","doi":"10.1080/17568919.2026.2718762","DOIUrl":"10.1080/17568919.2026.2718762","url":null,"abstract":"Chromanone and chromone are related benzopyran-based scaffolds that offer multiple opportunities for structural modification and medicinal chemistry. This review summarizes studies published from 2020 to 2026 on the synthesis, structure-activity relationships, biological activities, and developability of these compounds in cancer and metabolic disorders. Recent synthetic approaches have enabled the modification of the heterocyclic ring, fused benzene ring, and carbonyl region, as well as the preparation of hybrid, fused, and spiro derivatives of these compounds. In anticancer research, these compounds have demonstrated antiproliferative, pro-apoptotic, cell cycle-modulating, and signaling-related effects. In metabolic disorders, the reported activities of these compounds include the inhibition of carbohydrate-digesting enzymes, improvement of insulin signaling, suppression of hepatic glucose production, and regulation of lipid metabolism. The review also evaluated the strength of the available evidence, noting that many studies remain limited to docking, isolated enzyme assays, or cell-based screening. The available information on physicochemical properties, pharmacokinetics, metabolism, safety, and in vivo efficacy is comparatively limited. Future research should prioritize standardized biological evaluations, robust mechanistic validations, and integrated optimization of potency, selectivity, safety, and pharmacokinetic properties to facilitate the translational development of chromanone- and chromone-based compounds.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2601-2620"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790670","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}

引用次数: 0

Progress and challenges in the design and development of selective KRAS G12D-targeted drug discovery: inhibitors, degraders and emerging therapeutic strategies. 选择性KRAS g12d靶向药物的设计和开发进展与挑战：抑制剂、降解剂和新兴治疗策略。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-19 DOI: 10.1080/17568919.2026.2719780

Eunhye Jeon, Jaewon Song, Taebo Sim

{"title":"Progress and challenges in the design and development of selective KRAS G12D-targeted drug discovery: inhibitors, degraders and emerging therapeutic strategies.","authors":"Eunhye Jeon, Jaewon Song, Taebo Sim","doi":"10.1080/17568919.2026.2719780","DOIUrl":"10.1080/17568919.2026.2719780","url":null,"abstract":"KRAS is one of the most frequently mutated oncogenes in human cancers, with KRAS G12D representing the predominant mutation in pancreatic ductal adenocarcinoma and a major driver of colorectal and lung cancers. Although KRAS was long considered \"undruggable\" due to structural and biochemical constraints, the discovery of the switch-II pocket enabled the development of direct KRAS inhibitors, leading to the clinical success of KRAS G12C-targeted therapies. Building on this breakthrough, advances have been made in KRAS G12D-targeted drug development, including potent non-covalent inhibitors such as MRTX1133, HRS-4642, LY3962673, and INCB161734, as well as RAS(ON) tri-complex inhibitors such as RMC-9805. Pan-RAS and pan-KRAS inhibitors have emerged as a promising strategy to overcome the limitations of mutation-specific KRAS inhibitors, including restricted mutation coverage and acquired resistance. Among the developed pan-RAS inhibitors, RMC-6236 is the most advanced candidate in clinical development. In parallel, targeted protein degradation strategies, particularly PROTAC-based degraders such as ASP3082 and RP03707, have emerged as promising alternatives to overcome resistance and improve therapeutic durability. Combination strategies involving EGFR inhibitors, chemotherapy, and immunotherapy are also expanding clinical potential. This review summarizes recent progress in KRAS G12D-targeted inhibitors and degraders, highlighting current challenges and future opportunities for improving KRAS-directed cancer treatment.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2585-2600"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790699","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}

引用次数: 0

Harnessing the quinoline core for targeted cancer therapy. 利用喹啉核心进行靶向癌症治疗。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-13 DOI: 10.1080/17568919.2026.2718761

Cong-Jun Liu, Wei-Wen Huang, Jun-Jie Wang, Wen-Shuo Jiang, Xin-Yue Zhang, Xin Chen, Ya Gao, Xing-Jie Dai

引用次数: 0

Rational drug design for Alzheimer's disease: from approved therapies to next-generation clinical candidates and AI-guided innovation. 阿尔茨海默病的合理药物设计：从批准的疗法到下一代临床候选药物和人工智能引导的创新。

IF 3.3 4区医学

Future medicinal chemistry Pub Date : 2026-09-01 Epub Date: 2026-08-10 DOI: 10.1080/17568919.2026.2714022

Sana Saffour, Turgut Seckin Gul, Halise Inci Gul

{"title":"Rational drug design for Alzheimer's disease: from approved therapies to next-generation clinical candidates and AI-guided innovation.","authors":"Sana Saffour, Turgut Seckin Gul, Halise Inci Gul","doi":"10.1080/17568919.2026.2714022","DOIUrl":"10.1080/17568919.2026.2714022","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by multifactorial pathology, including amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, and synaptic dysfunction. Despite extensive research, currently approved treatment provides only symptomatic relief, while recently approved disease-modifying monoclonal antibodies have shown limited benefits. Ongoing clinical investigations have shifted toward multi-target directed ligands (MTDLs), RNA-based therapies, immunotherapies, and vaccines. Some approved drugs that have established safety profiles are being repurposed to address the disease's neuropsychiatric symptoms or modulate AD pathological changes. Integrating diverse pharmacophores, such as curcumin, resveratrol, chromone, and indole, within a single skeleton is anticipated to exert multi-modal modifying properties. In parallel, optimization of ADME properties, particularly blood-brain barrier (BBB) permeation and efflux modulation, remains a major obstacle in AD drug design. The incorporation of artificial intelligence (AI) and machine learning (ML) is expected to enhance the prediction of pharmacokinetic, pharmacodynamic, and toxicity parameters.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2425-2443"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701110","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}

引用次数: 0