Future medicinal chemistry最新文献

Recent advances and future perspectives in small molecule JAK2 inhibitors. 小分子JAK2抑制剂的研究进展及未来展望

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-20 DOI: 10.1080/17568919.2025.2507564

Muhammad Yasir, Jongseon Choe, Mubashir Hassan, Andrzej Kloczkowski, Wanjoo Chun

{"title":"Recent advances and future perspectives in small molecule JAK2 inhibitors.","authors":"Muhammad Yasir, Jongseon Choe, Mubashir Hassan, Andrzej Kloczkowski, Wanjoo Chun","doi":"10.1080/17568919.2025.2507564","DOIUrl":"https://doi.org/10.1080/17568919.2025.2507564","url":null,"abstract":"The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signaling pathway is essential for controlling immune function, blood cell formation, and cell growth. Dysregulation of this pathway is implicated in various diseases, including hematologic malignancies, autoimmune disorders, and chronic inflammatory conditions. This review provides a comprehensive overview of the structural and functional aspects of JAK/STAT signaling, with a particular focus on the role of JAK2. This manuscript explores the primary regulators of the JAK/STAT pathway, such as Suppressors Of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS), and Protein Tyrosine Phosphatases (PTPs), which play a crucial role in maintaining cellular balance and stability. Additionally, the therapeutic landscape of JAK2 inhibitors is explored, covering both approved and investigational drugs, including their mechanisms of action, efficacy, and safety profiles. Emerging strategies such as drug repositioning using computational approaches and experimental validation are also highlighted. By integrating insights from molecular docking studies, machine learning models, and kinase assays, this review emphasizes the potential of JAK2 inhibitors in disease management.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-17"},"PeriodicalIF":3.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110356","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

Benzothiazole derivatives as inhibitors of chikungunya virus replicative cycle. 苯并噻唑衍生物对基孔肯雅病毒复制周期的抑制作用。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-16 DOI: 10.1080/17568919.2025.2504337

Shiraz Feferbaum-Leite, Natasha Marques Cassani, Uriel Enrique Aquino Ruiz, Renieidy Flávia Clemente Dias, Danilo Nascimento Farago, Marco Guevara-Vega, Nilson Nicolau-Junior, Robinson Sabino-Silva, Celso de Oliveira Rezende Júnior, Ana Carolina Gomes Jardim

{"title":"Benzothiazole derivatives as inhibitors of chikungunya virus replicative cycle.","authors":"Shiraz Feferbaum-Leite, Natasha Marques Cassani, Uriel Enrique Aquino Ruiz, Renieidy Flávia Clemente Dias, Danilo Nascimento Farago, Marco Guevara-Vega, Nilson Nicolau-Junior, Robinson Sabino-Silva, Celso de Oliveira Rezende Júnior, Ana Carolina Gomes Jardim","doi":"10.1080/17568919.2025.2504337","DOIUrl":"https://doi.org/10.1080/17568919.2025.2504337","url":null,"abstract":"Aims: Chikungunya virus (CHIKV) is the agent of chikungunya fever (CHIKF), a reemerging disease prevalent in tropical regions. With no licensed treatments available, identifying effective antiviral compounds is critical. This study evaluates the antiviral potential of 20 synthetic sulfonamide derivatives against CHIKV.Methodology: We tested 13 heteroaromatic derivatives containing thiazole, benzimidazole, and benzothiazole (BTA) moieties, along with seven sulfonamides bearing ester and carboxylic acid groups. CHIKV-nanoluc replication was assessed in vitro, and molecular docking and infrared spectroscopy studies were conducted to explore interactions with viral proteins.Results: BTA derivatives 6, 9, 11, and 13 demonstrated potent CHIKV inhibition, with EC50 values between 14.9 and 63.1 µM and selective indexes of 13.8, 5.8, 4.4, and 11, respectively. All compounds acted in the virus post-entry stage, with compound 9 reducing viral replication by 98%. Compound 9 exhibited multi-stage activity, inhibiting CHIKV through virucidal (55%), pre-treatment (69%), and entry (98%) mechanisms. Molecular docking suggested strong binding affinities to CHIKV non-structural proteins and envelope glycoproteins. Infrared spectroscopy corroborated compound 9's interaction with the glycoprotein complex and lipids.Conclusions: These findings highlight BTA derivatives as promising CHIKV inhibitors. Compound 9's ability to interfere at multiple stages of infection suggests its potential for therapeutic development against CHIKF.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077140","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

Design, development, and therapeutic applications of rhenium tricarbonyl complexes. 三羰基铼配合物的设计、开发和治疗应用。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-15 DOI: 10.1080/17568919.2025.2504324

Rajesh Kushwaha, Samya Banerjee

引用次数: 0

Design and synthesis of newer 5-aryl-N-(naphthalen-2-yl)-1,3,4-oxadiazol-2-amine analogues as anticancer agents. 新型抗癌药物5-芳基- n-（萘-2-基）-1,3,4-恶二唑-2-胺类似物的设计与合成。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-15 DOI: 10.1080/17568919.2025.2504335

Mohamed Jawed Ahsan, Vivek Kumar, Amena Ali, Abuzer Ali, Mohammad Yusuf, Iqrar Ahmad, Harun Patel, Salahuddin, Md Faiyaz Ahsan

{"title":"Design and synthesis of newer 5-aryl-N-(naphthalen-2-yl)-1,3,4-oxadiazol-2-amine analogues as anticancer agents.","authors":"Mohamed Jawed Ahsan, Vivek Kumar, Amena Ali, Abuzer Ali, Mohammad Yusuf, Iqrar Ahmad, Harun Patel, Salahuddin, Md Faiyaz Ahsan","doi":"10.1080/17568919.2025.2504335","DOIUrl":"https://doi.org/10.1080/17568919.2025.2504335","url":null,"abstract":"Aim: Cancer is the second leading cause of death and chemotherapy is widely used and well-known for treating cancer, yet it has lots of adverse side effects, making the search for novel compounds imperative. We reported here design, synthesis, DFT analysis, anticancer evaluation and in-silico studies of new 1,3,4-oxadiazoles (4a-e).Material and methods: IMC-038525 and IMC-094332 tubulin inhibitors' oxadiazole-linked aryl cores inspired the innovative compounds, and synthesis was accomplished in two steps followed by their characterization by spectral data. The HOMO and LUMO energy gap (ΔE) was determined to investigate compounds' (4a-e) stability followed by their anticancer activity at 10 μM and in-silico studies.Results and conclusion: 5-(4-Nitrophenyl)-N-(naphthalene-2-yl)-1,3,4-oxadiazol-2-amine (4b) demonstrated substantial anticancer activity against a few cell lines like SR, MDA-MB-435, MOLT-4, K-562, and HL-60(TB). 5-(3,4,5-Trimethoxyphenyl)-N-(naphthalene-2-yl)-1,3,4-oxadiazol-2-amine (4e) demonstrated promising anticancer activity against cell lines, UO-31, NCI-H226, CAKI-1, PC-3, and MCF7. The molecular docking against tubulin's colchicine binding site (PDB ID: 1AS0), displayed a docking score of -7.295 Kcal/mol and a H-bond interaction with Ala317 residue for the ligand 4e. The ligand 4e was found to interacted 24 amino acids of the tubulin protein in MD simulation investigation with moderate local conformational changes with ligand 4e (< 1 Å).","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077146","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, antimicrobial evaluation, HPLC-based compound accumulation and docking studies of 2-methoxybenzoyl thioureas. 2-甲氧基苯甲酰硫脲的合成、抗菌评价、hplc积累及对接研究

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-15 DOI: 10.1080/17568919.2025.2504332

Sule Erol Gunal, Selen Duygu Çeçen, Engin Kaplan

{"title":"Synthesis, antimicrobial evaluation, HPLC-based compound accumulation and docking studies of 2-methoxybenzoyl thioureas.","authors":"Sule Erol Gunal, Selen Duygu Çeçen, Engin Kaplan","doi":"10.1080/17568919.2025.2504332","DOIUrl":"https://doi.org/10.1080/17568919.2025.2504332","url":null,"abstract":"Introduction: In this study, we presented the synthesis, antimicrobial activity, High Performance Liquid Chromatography (HPLC)-based compound accumulation and molecular docking of 2-methoxybenzoyl substituted thiourea derivatives.Materials and methods: The antimicrobial activity of a total of eight synthesized compounds was evaluated against seven species of bacteria and fungi. HPLC-based compound accumulation assay, molecular docking, in silico toxicity and ADME analyses were performed for selected compounds for further evaluation of compound activity relationship.Results and discussion: The compounds exhibited greater activity against fungi than bacteria, with compounds 1b, 1c, 1d, and 1g showing particularly strong activity against Candida species. Compounds 1a, 1b, 1d, and 1h that had varying biological activities were selected for further analyses. Compounds 1a, 1b, 1d, and 1h accumulated intracellularly reaching up to 36.77% within 1 hours. Molecular docking studies revealed compatible interactions among the compounds in comparison to their varying biological activities. Additionally, all compounds had low toxicity and showed no physicochemical violations when compared to Lipinski's rule of five.Conclusion: The results suggest that optimizing the position of substituents on the phenyl rings of acyl thioureas could enhance the antimicrobial activity of our compounds.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077187","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

An insight into the in vivo antitumor therapeutic potential of indole-(fused) pyri(mi)dine hybrids. 深入了解吲哚-（融合）吡啶（mi）dine杂合体的体内抗肿瘤治疗潜力。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-14 DOI: 10.1080/17568919.2025.2504336

Zhi Xu, Rongqiang Li, Kexin Ding, Yiling Wang, Yafei Zhuang

{"title":"An insight into the in vivo antitumor therapeutic potential of indole-(fused) pyri(mi)dine hybrids.","authors":"Zhi Xu, Rongqiang Li, Kexin Ding, Yiling Wang, Yafei Zhuang","doi":"10.1080/17568919.2025.2504336","DOIUrl":"https://doi.org/10.1080/17568919.2025.2504336","url":null,"abstract":"Cancer can invade and destroy any part of the body, representing a grand social, public health, and economic challenge. Chemotherapy plays a crucial role in cancer treatment, and in recent decades, hundreds of anticancer chemotherapeutics have been introduced. Nevertheless, multidrug resistance and side effects are the main obstacles to successful cancer therapy, highlighting the pressing requirement for the development of new chemotherapeutics to address the above issues. Indole hybrids not only have the potential to surmount drug resistance and adverse effects caused by individual components but also can enhance efficacy and improve pharmacokinetic characteristics since hybrid molecules can concurrently regulate multiple targets within cancer cells. Moreover, numerous indole hybrids exemplified by mobocertinib (indole-pyrimidine hybrid) and osimertinib (indole-quinazoline hybrid) have already been utilized in clinical cancer treatment. Therefore, indole hybrids have emerged as valuable scaffolds for the treatment and eradication of cancer. This review aims to elucidate the current landscape of indole-(fused) pyri(mi)dine hybrids, including indole-quinolines/quinolinones, indole-pyridines, indole-pyrimidines, and indole-fused pyrimidines, with in vivo antitumor therapeutic potential, offering effective candidates for in-depth preclinical evaluations, encompassing articles published from 2021 onward.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-19"},"PeriodicalIF":3.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077206","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

Key breakthroughs in small molecule MYC inhibitors. 小分子MYC抑制剂的关键突破。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-12 DOI: 10.1080/17568919.2025.2504325

Rafaelo Dhimitriu, Helena Tsimpili, Grigoris Zoidis

引用次数: 0

Coumarin hybrids: dual-target candidates for future antimicrobial and antitubercular therapies. 香豆素混合物：未来抗菌和抗结核治疗的双靶点候选者。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-12 DOI: 10.1080/17568919.2025.2504331

Abhay Bavishi, Hardev Vala, Shailesh Thakrar, Sagar Swami, Dhiman Sarkar, Rushit Shukla, Jignesh Kamdar, Anamik Shah

{"title":"Coumarin hybrids: dual-target candidates for future antimicrobial and antitubercular therapies.","authors":"Abhay Bavishi, Hardev Vala, Shailesh Thakrar, Sagar Swami, Dhiman Sarkar, Rushit Shukla, Jignesh Kamdar, Anamik Shah","doi":"10.1080/17568919.2025.2504331","DOIUrl":"https://doi.org/10.1080/17568919.2025.2504331","url":null,"abstract":"Aims: This study aimed to synthesize, characterize, and evaluate the antimicrobial and antitubercular activities of two novel series of coumarin-based derivatives (Series 5 and Series 9), focusing on their structure-activity relationship (SAR) and molecular docking interactions with key bacterial enzymes.Materials & methods: Series 5 (5a-5j) and Series 9 (9a-9t) compounds were synthesized and characterized using spectroscopic techniques. Their antimicrobial and antitubercular activities were evaluated against Mycobacterium tuberculosis, Staphylococcus aureus, Bacillus subtilis, and E. coli. IC₅₀ values were determined, and molecular docking studies were conducted to assess binding interactions with M. tuberculosis enoyl-ACP reductase (InhA) and E. coli DNA gyrase B.Results: Series 5 compounds exhibited moderate activity, with 5f, 5 g, 5i, and 5j showing notable inhibition. Series 9 derivatives displayed superior dual-target inhibition, with 9t, 9c, 9a, 9b, and 9p achieving >90% inhibition against S. aureus and B. subtilis. The lowest IC₅₀ against M. tuberculosis was observed for 9c (1.50 µg/mL), followed by 9a (2.84 µg/mL) and 9b (2.73 µg/mL). Molecular docking confirmed strong binding interactions, correlating with observed biological activities.Conclusions: Series 9 compounds, particularly 9t, 9c, and 9a, demonstrate high potential as dual-target antimicrobial drug candidates. Further optimization may enhance their therapeutic efficacy.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973083","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

Methoxy group: a non-lipophilic "scout" for protein pocket finding. 甲氧基：寻找蛋白质口袋的非亲脂性“侦察兵”。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-04-03 DOI: 10.1080/17568919.2025.2485865

Debora Chiodi, Yoshihiro Ishihara

引用次数: 0

Unveiling the research directions for pyrrolidine-based small molecules as versatile antidiabetic and anticancer agents. 揭示了吡咯烷基小分子多功能抗糖尿病和抗癌药物的研究方向。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-05-01 Epub Date: 2025-05-12 DOI: 10.1080/17568919.2025.2501923

Shiv Kumar, Rupali Kohal, Debarshi Mondal, Shreya Kumari, Preety Kumari, Priya Bisht, Ghanshyam Das Gupta, Sant Kumar Verma

{"title":"Unveiling the research directions for pyrrolidine-based small molecules as versatile antidiabetic and anticancer agents.","authors":"Shiv Kumar, Rupali Kohal, Debarshi Mondal, Shreya Kumari, Preety Kumari, Priya Bisht, Ghanshyam Das Gupta, Sant Kumar Verma","doi":"10.1080/17568919.2025.2501923","DOIUrl":"10.1080/17568919.2025.2501923","url":null,"abstract":"The pyrrolidine moiety, a five-membered saturated nitrogen-containing heterocycle, emerged as a crucial pharmacophore in medicinal chemistry due to its distinctive physicochemical properties, including hydrophilicity, basicity, and structural rigidity. Extensive modifications of pyrrolidine derivatives yielded novel compounds with pronounced antidiabetic and anticancer activities. The structural investigation of pyrrolidine-based molecules demonstrated that substitutions at the N1, 3rd, and 5th positions offer significant opportunities for optimizing biological activity and enhancing target-specific interactions. The synthesis of pyrrolidine-based molecules has been explored in literature; however, structural, target interaction analysis, and pharmacological aspects warranted for the development of targeted small molecule versatile antidiabetic and anticancer agents are lacking. The review addresses this gap by emphasizing the developments in pyrrolidine-based small molecules via structural and target interaction analysis, highlighting their antidiabetic and anticancer activities, and offering a comprehensive perspective on the development of targeted therapeutics. The investigated structural features and pharmacological developments underscore the dual functionality of pyrrolidine-based drugs in managing disorders, such as diabetes and cancer, that share common pathological mechanisms, such as inflammation, oxidative stress, and metabolic dysregulation. This overlap has catalyzed the development of multifunctional pyrrolidine derivatives capable of targeting pathways integral to both conditions, providing a promising avenue for therapeutic innovation.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1039-1053"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987698","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