Future medicinal chemistry最新文献_第4页

Research landscape of hydroxamic acid hybrids with therapeutic potential against prostate cancer: a decade of advances. 具有治疗前列腺癌潜力的羟肟酸混合物的研究前景：十年的进展。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-08-28 DOI: 10.1080/17568919.2025.2552634

Jing Fan, Rui-Hong Wu, He Li, Chao Wang, Ling-Zhi Chen, Lian-Shun Feng

{"title":"Research landscape of hydroxamic acid hybrids with therapeutic potential against prostate cancer: a decade of advances.","authors":"Jing Fan, Rui-Hong Wu, He Li, Chao Wang, Ling-Zhi Chen, Lian-Shun Feng","doi":"10.1080/17568919.2025.2552634","DOIUrl":"10.1080/17568919.2025.2552634","url":null,"abstract":"Prostate cancer, a malignant tumor arising from the prostate gland, ranks as one of the most commonly diagnosed cancers in men globally and the eighth leading cause of cancer-related mortality worldwide. Hydroxamic acid derivatives, identified as outstanding histone deacetylase (HDAC) inhibitors, are a class of compounds with significant research interest in prostate cancer due to their diverse mechanisms of action, primarily involving epigenetic regulation and targeted enzyme inhibition. Recent studies highlight that incorporating diverse anti-prostate cancer pharmacophores with a hydroxamic acid moiety can potentiate their inhibitory efficacy against HDACs or endow them with multi-target HDAC inhibitory capabilities. Furthermore, hydroxamic acid hybrids possess inherent potential to enhance therapeutic efficacy through multi-target engagement, circumvent drug resistance via epigenetic reprogramming, improve pharmacokinetic profiles through structural optimization, and mitigate off-target toxicity through enhanced receptor selectivity, representing promising scaffolds for designing novel therapeutic candidates against prostate cancer. This review comprehensively outlines the research landscape of hydroxamic acid hybrids with therapeutic potential in prostate cancer, spanning from 2016 to the present, to uncover new avenues for discovering novel therapeutic candidates.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2179-2191"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949335","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

Half-life prediction of central nervous system (CNS) small molecules in humans using gradient tree boosting. 用梯度树增强法预测人类中枢神经系统（CNS）小分子半衰期。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-09-07 DOI: 10.1080/17568919.2025.2557178

Hong Wang, Pan Zhang, Stephen J Barigye, James R Empfield, Steven S Wesolowski

{"title":"Half-life prediction of central nervous system (CNS) small molecules in humans using gradient tree boosting.","authors":"Hong Wang, Pan Zhang, Stephen J Barigye, James R Empfield, Steven S Wesolowski","doi":"10.1080/17568919.2025.2557178","DOIUrl":"10.1080/17568919.2025.2557178","url":null,"abstract":"Aims: To develop a machine learning (ML) model for early-stage prediction of human half-life of oral central nervous system (CNS) drugs and to establish a curated dataset, including key in vitro and in vivo data, to support future modeling efforts.Materials & methods: Human and rat half-life, plasma protein binding (PPB), and liver microsomal clearance (LM) data for 76 diverse CNS drugs and candidates were obtained from public sources or evaluated at WuXi AppTec. Gradient tree boosting (GTB) models were constructed using ChemAxon's Trainer Engine. Feature importance was assessed, and model performance was evaluated on an external validation set.Results: The best-performing model achieved 82.4% of predictions within two-fold of observed values, with a coefficient of determination (R2) of 0.75 and a root mean square error (RMSE) of 0.25. Good generalizability was confirmed using similarity-based data splitting and Y-randomization. Integration of in vitro features, preclinical in vivo data, and physicochemical properties substantially improved predictive performance. Key features driving accurate human half-life prediction were identified.Conclusion: This model demonstrates practical applications for early-stage prediction of human half-life and prioritization of CNS drug candidates. The curated dataset offers a valuable resource to enhance internal databases and advance more robust predictive models.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2213-2219"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014608","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

Enhancing thiazolide efficacy: C-4 aryl modifications drive selective SARS-CoV-2 inhibition. 增强噻唑类药物疗效：C-4芳基修饰驱动选择性抑制SARS-CoV-2。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-09-15 DOI: 10.1080/17568919.2025.2559572

Rizwan Bashir, Sobia Jabeen, Wasim Abbas, Fazal-E Habib, Shoaib Iqbal, Moazur Rahman, Waqar Rauf, Mazhar Iqbal

{"title":"Enhancing thiazolide efficacy: C-4 aryl modifications drive selective SARS-CoV-2 inhibition.","authors":"Rizwan Bashir, Sobia Jabeen, Wasim Abbas, Fazal-E Habib, Shoaib Iqbal, Moazur Rahman, Waqar Rauf, Mazhar Iqbal","doi":"10.1080/17568919.2025.2559572","DOIUrl":"10.1080/17568919.2025.2559572","url":null,"abstract":"Background: COVID-19 highlighted urgent need for broad-spectrum antivirals. Nitazoxanide (NTZ), a broad-spectrum antiviral with an established safety profile, shows promise against SARS-CoV-2; however, its moderate potency and pharmacokinetic limitations necessitate the development of improved analogues.Methods: We synthesized 24 thiazolide analogues, including novel molecules bearing 4´- or 5´-aryl substitutions, dual 4´,5´-modifications, or fused benzothiazole cores, and evaluated their in vitro efficacy against SARS-CoV-2 (Vero E6 cells). Antiviral potency (IC50), cytotoxicity (CC50), and selectivity indices (SI = CC50/IC50) were determined by qRT-PCR and MTT assays. In silico ADMET profiling predicted drug-likeness, absorption, distribution, metabolism, excretion, and toxicity.Results: Among the analogues, 4´-aryl thiazolides (6d-6 g) and one dual-substituted thiazolide (7b) exhibited outstanding selectivity index (SI > 30), significantly surpassing NTZ (SI ≈ 14). The analogue 6e (3-OCF3-phenyl) demonstrated the highest SI of ≈ 51 (IC50 ≈0.21 µM; CC50 ≈10.8 µM). Benzothiazole analogue 8a (OCF3 at 4´-position) also showed favorable SI (≈11). ADMET predictions confirmed acceptable oral bioavailability, minimal cytochrome P450 (CYP450) inhibition, and low cardiotoxicity risk.Conclusions: Lipophilic, electron-withdrawing substituents at C-4 of the thiazole core markedly enhance antiviral potency and therapeutic potential. In particular, 4´-(PhOCF3) substitutions emerge as lead scaffolds for further preclinical development. These insights provide a way forward for optimizing thiazolides against SARS-CoV-2 and other emerging viruses.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2235-2250"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063968","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

Organotellurium(IV) complexes disrupt microbes via quantum insights into antioxidant and antimicrobial activity. 有机碲（IV）配合物通过对抗氧化和抗菌活性的量子洞察破坏微生物。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-09-16 DOI: 10.1080/17568919.2025.2559571

Anisha Bhardwaj, Amit Dubey, Aisha Tufail, Magda H Abdellattif, Manish Kumar, Sapana Garg

{"title":"Organotellurium(IV) complexes disrupt microbes via quantum insights into antioxidant and antimicrobial activity.","authors":"Anisha Bhardwaj, Amit Dubey, Aisha Tufail, Magda H Abdellattif, Manish Kumar, Sapana Garg","doi":"10.1080/17568919.2025.2559571","DOIUrl":"10.1080/17568919.2025.2559571","url":null,"abstract":"Aims: This study aimed to synthesize and characterize novel thiophene-based Schiff base organotellurium(IV) complexes and evaluate their antioxidant and antimicrobial potential through combined experimental and computational approaches.Materials & methods: The Schiff base ligand (3MTCPT) and its tellurium(IV) complexes (7a-7f) were synthesized and characterized using FT-IR, UV-Vis, NMR, mass spectrometry, SEM-EDAX, and powder-XRD. Computational studies included Density Functional Theory (DFT), molecular docking, molecular dynamics (MD) simulations, pharmacophore modeling, and ADMET predictions. Antioxidant activity was assessed by the DPPH assay, while antimicrobial efficacy was tested against bacterial (E. coli, P. aeruginosa, S. aureus, B. subtilis) and fungal (C. albicans, A. niger) strains.Results: DFT calculations (B3LYP/def2-TZVP) revealed reduced HOMO-LUMO band gaps for the complexes (1.7-2.1 eV) compared with the free ligand (3.47 eV), confirming enhanced reactivity. Complex 7d exhibited strong antioxidant activity (IC₅₀ = 68.56 µg/mL), comparable to ascorbic acid, while complex 7f showed potent antibacterial activity (MIC = 25 µg/mL against E. coli), supported by favorable docking interactions (-151.51 kcal/mol) and MD stability. ADMET analysis predicted favorable pharmacokinetics. .Conclusion: The organotellurium(IV) complexes demonstrated significant antioxidant and antimicrobial activities, validated experimentally and theoretically, highlighting their potential as next-generation organometallic therapeutics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2197-2212"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069487","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

Discovery of new thiadiazole-based VEGFR-2 inhibitors: design, synthesis, cytotoxicity, and apoptosis induction. 新型噻二唑类VEGFR-2抑制剂的发现：设计、合成、细胞毒性和凋亡诱导。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-08-29 DOI: 10.1080/17568919.2025.2552639

Eslam B Elkaeed, Walid E Elgammal, Hazem Elkady, Hazem A Mahdy, Aisha A Alsfouk, Dalal Z Husein, Omar A Soliman, Mariam Omara, Ibrahim H Eissa, Ahmed M Metwaly

{"title":"Discovery of new thiadiazole-based VEGFR-2 inhibitors: design, synthesis, cytotoxicity, and apoptosis induction.","authors":"Eslam B Elkaeed, Walid E Elgammal, Hazem Elkady, Hazem A Mahdy, Aisha A Alsfouk, Dalal Z Husein, Omar A Soliman, Mariam Omara, Ibrahim H Eissa, Ahmed M Metwaly","doi":"10.1080/17568919.2025.2552639","DOIUrl":"10.1080/17568919.2025.2552639","url":null,"abstract":"Background: Vascular endothelial growth factor receptor-2 (VEGFR-2) is a validated target in cancer therapy. However, approved inhibitors like sorafenib are often limited by off-target toxicity and resistance. This study aimed to develop novel thiadiazole-based VEGFR-2 inhibitors with improved selectivity and safer profiles.Methods: A series of 2,3-dihydro-1,3,4-thiadiazole derivatives was rationally designed, synthesized, and structurally characterized. In vitro cytotoxicity was assessed against MCF-7, HepG-2, HCT-116, and normal WI-38 cells. Mechanistic assays included flow cytometry for cell cycle and apoptosis, and ELISA for caspase-3, Bcl-2, and Bax expression. Molecular docking, 200-ns molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and in silico toxicity profiling supported experimental findings.Results: Compound 11a exhibited the most potent and selective activity (IC₅₀: 9.49 µM for MCF-7, 12.89 µM for HepG-2; SI > 3). It induced >70% apoptosis and dual-phase (S and G2/M) cell cycle arrest. VEGFR-2 inhibition (IC₅₀ = 0.055 µM) was comparable to sorafenib. Computational studies confirmed stable binding at VEGFR-2 active sites.Conclusion: Compound 11a is a promising thiadiazole-based candidate with notable in vitro potency, selectivity, and mechanistic activity, supporting its potential for further pharmacokinetics/toxicity evaluation and structural refinement as a VEGFR-2-targeted agent.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2145-2162"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949351","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

Synthetic approaches and therapeutic potential of thiophene derivatives as COX and LOX inhibitors. 噻吩衍生物作为COX和LOX抑制剂的合成方法和治疗潜力。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-09-07 DOI: 10.1080/17568919.2025.2557184

Suman Lata, Shivani Bharti, Komalpreet Kaur, Amit Pandit, Vikrant Abbot

{"title":"Synthetic approaches and therapeutic potential of thiophene derivatives as COX and LOX inhibitors.","authors":"Suman Lata, Shivani Bharti, Komalpreet Kaur, Amit Pandit, Vikrant Abbot","doi":"10.1080/17568919.2025.2557184","DOIUrl":"10.1080/17568919.2025.2557184","url":null,"abstract":"Thiophene derivatives have gained considerable interest lately due to their potential as anti-inflammatory agents. Their structural flexibility and capacity to interact with key enzymes involved in inflammatory processes position them as promising candidates for drug development. This review provides a comprehensive overview of the latest research, focusing on the synthesis and therapeutic evaluation of thiophene-based compounds that act as inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. It discusses synthetic methodologies, structure-activity relationship (SAR) patterns, and the biological activities of these compounds, with a particular focus on those demonstrating dual COX/LOX inhibition. By consolidating recent findings, the review aims to enhance ongoing efforts to develop more effective and safer anti-inflammatory agents that utilize thiophene as a core scaffold. By summarizing research data from 2018 to 2025 using databases such as Google Scholar, Web of Science, PubMed, and Scopus, this review article aims to contribute to the development of novel lead molecules, offer promising avenues for future drug discovery, and therapeutic innovation in inflammation-related diseases.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2251-2279"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014590","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

Structure-aware diffusion model for molecule generation based on K-Nearest Neighbor and equivariant graph neural network. 基于k近邻和等变图神经网络的分子生成结构感知扩散模型。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-09-03 DOI: 10.1080/17568919.2025.2552638

Xin Zeng, Peng-Kun Feng, Shu-Juan Li, Pei-Yan Meng, Wen-Feng Du, Bei Jiang, Zi-Zhong Yang, Yi Li

{"title":"Structure-aware diffusion model for molecule generation based on K-Nearest Neighbor and equivariant graph neural network.","authors":"Xin Zeng, Peng-Kun Feng, Shu-Juan Li, Pei-Yan Meng, Wen-Feng Du, Bei Jiang, Zi-Zhong Yang, Yi Li","doi":"10.1080/17568919.2025.2552638","DOIUrl":"10.1080/17568919.2025.2552638","url":null,"abstract":"Aim: Generating molecules with specific chemical properties for target proteins can accelerate the drug development process and open new avenues for developing treatments for diseases with known pathogenic target proteins. However, current approaches to generate molecules with desired properties face several challenges, including prolonged generation time, complexity in learning parameters, and unqualified chemical properties.Results/methodology: To address these issues, we proposed a structure-aware diffusion model, termed KGMG. This method incorporated the protein pocket as a constraint and integrated cutting-edge technologies such as KNN (K-Nearest Neighbors), equivariant graph neural networks, and self-attention mechanism. The core concept of KGMG was based on the 3D point cloud representation of protein pocket and its bound molecule. First, KNN was employed to construct both local and global graphs for each atom, followed by the uses of equivariant graph neural networks to iteratively update the atomic features and coordinates. Next, a self-attention mechanism was applied to fuse the updated atomic features and coordinates, forming the forward propagation process of diffusion model.Conclusion: Finally, through a backward denoising process, the model progressively restored the data, generating new molecules for a specific target protein. KGMG exhibited superior performance across multiple evaluation metrics.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2119-2130"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949217","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

Recent progress in the synthetic and medicinal perspective of imidazo[2,1-b]thiazole derivatives. 咪唑[2,1-b]噻唑衍生物的合成及药用前景研究进展。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-09-01 Epub Date: 2025-08-30 DOI: 10.1080/17568919.2025.2552637

Virendra Santosh Amrutkar, Rakesh Khator, Vikramdeep Monga

{"title":"Recent progress in the synthetic and medicinal perspective of imidazo[2,1-b]thiazole derivatives.","authors":"Virendra Santosh Amrutkar, Rakesh Khator, Vikramdeep Monga","doi":"10.1080/17568919.2025.2552637","DOIUrl":"10.1080/17568919.2025.2552637","url":null,"abstract":"Imidazo[2,1-b]thiazole represents a privileged heterocyclic moiety in medicinal chemistry which garnered huge attention among the researchers because of its extensive biological properties and ease of synthetic feasibility. Substituted imidazo[2,1-b]thiazole analogs with diverse therapeutic outcomes play a crucial role in the cure or management of various human ailments. The impact of this moiety in drug discovery can be realized from the fact that drugs based on this scaffold are used clinically. Medicinal and synthetic chemists have widely explored the chemical space around this scaffold for the generation of novel molecules capable of interacting with different biological targets of therapeutic concern. Due to its fascinating pharmacological profile, chemists have unfolded different facile and efficient synthetic protocols for imidazo[2,1-b]thiazole-based molecules. The present review highlights its outstanding role in drug discovery including different approaches for the synthesis of imidazo[2,1-b]thiazole hybrids. The recent advancements in the medicinal chemistry of imidazo[2,1-b]thiazole based analogs along with structure-activity relationships (SARs) and molecular docking studies have been compiled. The present review provides valuable insights for the design and development of imidazo[2,1-b]thiazole based bioactive agents as potential therapeutic candidates with desired efficacy and safety profile.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"2163-2177"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144949302","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

Correction. 修正。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-08-26 DOI: 10.1080/17568919.2025.2552567

引用次数: 0

Novel di-aryl chalcone derived pyrazole linked to methane sulfonyl pharmacophore as potent selective COX-2 inhibitors; design, synthesis, molecular modeling, in vitro and in vivo anti-inflammatory activities. 新型甲烷磺酰基药效团二芳基查尔酮衍生吡唑作为选择性COX-2抑制剂设计、合成、分子建模，体外和体内抗炎活性。

IF 3.4 4区医学

Future medicinal chemistry Pub Date : 2025-08-01 Epub Date: 2025-08-17 DOI: 10.1080/17568919.2025.2545171

Abeer M Abd El-Hameed, Ahmed H Lotfallah, Mohamed T M Nemr, Hoda Khalifa Abdelhady, Haredy Hassan Haredy, Ahmed M Sayed, Mamdouh F A Mohamed, Deiaa E Elsayed Abouzed, Wael A A Fadaly

{"title":"Novel di-aryl chalcone derived pyrazole linked to methane sulfonyl pharmacophore as potent selective COX-2 inhibitors; design, synthesis, molecular modeling, in vitro and in vivo anti-inflammatory activities.","authors":"Abeer M Abd El-Hameed, Ahmed H Lotfallah, Mohamed T M Nemr, Hoda Khalifa Abdelhady, Haredy Hassan Haredy, Ahmed M Sayed, Mamdouh F A Mohamed, Deiaa E Elsayed Abouzed, Wael A A Fadaly","doi":"10.1080/17568919.2025.2545171","DOIUrl":"10.1080/17568919.2025.2545171","url":null,"abstract":"Aim: Based on the structural features of both lonazolac and celecoxib, as an attempt to improve COX-2 selectivity, a series of novel di-aryl-chalcone derived pyrazole (16a-l) was designed, synthesized, and evaluated for its COX-2 selective anti-inflammatory inhibitory activity.Results: Derivatives 16d, 16f, 16k, and 16l displayed approximately two-folds greater COX-2 inhibitory effects (IC50) than celecoxib, scoring IC50 of 0.446, 0.686, 0.348, and 0.771 μM, respectively, compared to 0.685 μM for celecoxib. 16d, 16f, 16k, and 16l compounds additionally demonstrated remarkable COX-2 selectivity index (S.I.) in the range of (S.I. = 25.56-70.40) in contrast to celecoxib (S.I. = 24.09). Moreover, In-vivo anti-inflammatory activity study of the most potent derivatives 16d, 16f, and 16k reinforced the in-vitro results. For instance, compound 16k induced 53% edema inhibition at the 5th hour, comparable to that observed with celecoxib. The compounds 16d, 16f, 16k, and 16l resulted in significant attenuation of pro-inflammatory mediators (PGE2, IL-6, TNF-α, and NF-Kβ) that produced from carrageenan-induced edema. Molecular docking and dynamics results of derivatives 16d, 16f, 16k, 16l indicate to their relatively stable interactions within the COX-2 active site.Conclusions: The present work paves the way for further development of potent selective COX-2 inhibitors with anti-inflammatory activity.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1849-1865"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872375","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