Future medicinal chemistry最新文献_第5页

A series of benzensulfonamide derivatives as new potent carbonic anhydrase IX and XII inhibitors. 一系列苯磺酰胺衍生物作为新型有效的碳酸酐酶IX和XII抑制剂。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-29 DOI: 10.1080/17568919.2025.2453420

Susanna Nencetti, Doretta Cuffaro, Lidia Ciccone, Alessio Nocentini, Miriana Di Stefano, Giulio Poli, Marco Macchia, Tiziano Tuccinardi, Elisa Nuti, Claudiu T Supuran, Armando Rossello, Elisabetta Orlandini

{"title":"A series of benzensulfonamide derivatives as new potent carbonic anhydrase IX and XII inhibitors.","authors":"Susanna Nencetti, Doretta Cuffaro, Lidia Ciccone, Alessio Nocentini, Miriana Di Stefano, Giulio Poli, Marco Macchia, Tiziano Tuccinardi, Elisa Nuti, Claudiu T Supuran, Armando Rossello, Elisabetta Orlandini","doi":"10.1080/17568919.2025.2453420","DOIUrl":"10.1080/17568919.2025.2453420","url":null,"abstract":"Aim: Human carbonic anhydrases (hCAs) are involved in many physiological processes including respiration, pH control, ion transport, bone resorption, and gastric fluid secretion. Recently, CA IX and CA XII have been studied for their role in cancer diseases, motivating the design of inhibitors of these isoforms.Material and method: Here, we used the tail approach to design a new series of monoaryl (1a-i) and bicyclic (1j-n) benzensulfonamide derivatives CA IX and CA XII inhibitors. All synthesized compounds were investigated toward a panel of hCAs, and most of them exhibited potent CA inhibitory activity for CA II, CA IX and CA XII with Ki values. In silico studies were performed to investigate the binding mode between inhibitors and CA.Results and conclusion: The best compound was 1i that showed a low nanomolar range of Ki value as CA inhibitor (Ki = 9.4, 5.6 and 6.3 nM hCA II, IX and XII, respectively).","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"271-285"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058210","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

Transition metal complexes: next-generation photosensitizers for combating Gram-positive bacteria. 过渡金属配合物：对抗革兰氏阳性细菌的下一代光敏剂。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-29 DOI: 10.1080/17568919.2025.2458459

Lingmin Pei, Xianyi Yu, Xiaoyu Shan, Guanying Li

{"title":"Transition metal complexes: next-generation photosensitizers for combating Gram-positive bacteria.","authors":"Lingmin Pei, Xianyi Yu, Xiaoyu Shan, Guanying Li","doi":"10.1080/17568919.2025.2458459","DOIUrl":"10.1080/17568919.2025.2458459","url":null,"abstract":"The rise of antibiotic-resistant Gram-positive bacterial infections poses a significant threat to public health, necessitating the exploration of alternative therapeutic strategies. A photosensitizer (PS) can convert energy from absorbed photon into reactive oxygen species (ROS) for damaging bacteria. This photoinactivation action bypassing conventional antibiotic mechanism is less prone to resistance development, making antibacterial photodynamic therapy (aPDT) highly efficient in combating Gram-positive bacteria. Photodynamic transition metal complexes leveraging the unique properties of metals to enhance the aPDT activity are the next-generation PS. This review provides an overview of metal-based PS for combating Gram-positive bacteria. Based on the structures, these metal-PS could be mainly classified as metal-tetrapyrrole derivatives, ruthenium complexes, iridium complexes, and zinc complexes. PS based on complexes of other transition metals such as silver, cobalt, and rhenium are also presented. Finally, we summarize the advantages and shortcomings of these metal- PS, conclude some critical aspects impacting their aPDT performances and give a perspective on their future development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"467-484"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058213","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

Facile synthesis, antimicrobial activity, and molecular docking analysis of 8-hydroxyquinoline-4-thiazolidinone hybrids. 8-羟基喹啉-4-噻唑烷酮杂合体的简单合成、抗菌活性及分子对接分析。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-02-14 DOI: 10.1080/17568919.2025.2463876

Jagruti Peddapaka, Aayesha Nasreen, Tulja Sanam, Mahammad Ghouse Shaik, Baijayantimala Swain, Shweta Sanwer, Ravi Alvala, Mohammed Arifuddin, Sridhar Goud Nerella

{"title":"Facile synthesis, antimicrobial activity, and molecular docking analysis of 8-hydroxyquinoline-4-thiazolidinone hybrids.","authors":"Jagruti Peddapaka, Aayesha Nasreen, Tulja Sanam, Mahammad Ghouse Shaik, Baijayantimala Swain, Shweta Sanwer, Ravi Alvala, Mohammed Arifuddin, Sridhar Goud Nerella","doi":"10.1080/17568919.2025.2463876","DOIUrl":"10.1080/17568919.2025.2463876","url":null,"abstract":"Background: 8-Hydroxyquinoline and 4-thiazolidinone derivatives are promising antimicrobial agents, recognized for their activity against resistant pathogens.Aim: The aim of this study is to develop 8-hydroxyquinoline-4-thiazolidinone derivatives as potential antimicrobial agents.Methods: Using a one-pot reaction with sodium tetrafluoroborate as an efficient and eco-friendly catalyst, compounds 6a - l were synthesized and subsequently screened for antibacterial and antifungal activity. Additionally, molecular docking and molecular dynamic simulations were performed to evaluate the active compounds and gain deeper insights into their potential as antimicrobial agents.Results: Compounds 6f and 6 g showed superior antibacterial activity to ciprofloxacin, particularly against Gram-negative bacteria, while 6b, 6 g, and 6 h demonstrated strong antifungal effects. Molecular docking, molecular dynamics simulations, and MM-GBSA calculations highlighted strong binding interactions and stable conformations of the active compounds within binding pocket of the FabZ enzyme. The ADMET analyses further indicated that these compounds possess favorable drug-like properties.Conclusion: The synthesized 8-hydroxyquinoline-4-thiazolidinone hybrids exhibit strong potential as broad-spectrum antimicrobial agents and merit further investigation as drug candidates.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"435-447"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413808","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

Key advances in the development of reversible covalent inhibitors. 可逆共价抑制剂的关键进展。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-19 DOI: 10.1080/17568919.2025.2453407

Faridoon, Jiyue Zheng, Guiping Zhang, Jie Jack Li

引用次数: 0

Benzo[a]phenoselenazine-based NIR photodynamic therapy for the treatment of COX-2 overexpressing cancer cells. 苯并[a]基于吩硒化嗪的近红外光动力疗法治疗COX-2过表达癌细胞。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-02-14 DOI: 10.1080/17568919.2025.2463878

Kalayou Hiluf Gebremedhin

{"title":"Benzo[a]phenoselenazine-based NIR photodynamic therapy for the treatment of COX-2 overexpressing cancer cells.","authors":"Kalayou Hiluf Gebremedhin","doi":"10.1080/17568919.2025.2463878","DOIUrl":"10.1080/17568919.2025.2463878","url":null,"abstract":"Background: Upregulation of Cyclooxygenase-2 (COX-2) in a variety of cancer cell lines, a key enzyme of prostaglandin biosynthesis, relative to surrounding normal tissues results in the use of the COX-2 protein as an attractive molecular target for many anticancer therapeutics. This could have a significant implication for selective destruction of cancer cells via the photodynamic therapy effects, leaving the normal tissue intact.Experimental: Here, a COX-2-specific NIR photosensitizer (Se-C6-IMC) was synthesized and developed by conjugating a classic anti-inflammatory drug indomethacin (IMC) as an efficient recognition group for COX-2 protein, with benzo[a]phenoselenazine derivative photosensitizer through hexanediamine linker.Result and discussion: In this study, Se-C6-IMC exhibited a strong NIR absorption in the phototherapeutic window, relatively high 1O2 generation (ΦΔ = 0.74 in CH2C2), and an excellent phototoxicity (IC50 = 0.04 µM, 14.4 J/cm2) against MCF-7 cells as compared to COS-7 cells lacking COX-2 protein expression.Conclusion: Se-C6-IMC showed the highest intracellular localization in Golgi apparatus, making it to more effective for cellular destruction and Golgi targeted therapy. Thus, Se-C6-IMC might hold great promise as a COX-2-specific NIR photosensitizer for improving the PDT efficiency and new Golgi-targeted PDT development in the future.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"425-434"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425214","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

The other side of the coin: protein deubiquitination by Ubiquitin-Specific Protease 1 in cancer progression and therapy. 硬币的另一面：泛素特异性蛋白酶1在癌症进展和治疗中的蛋白质去泛素化。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-17 DOI: 10.1080/17568919.2025.2453414

Xinlan Hu, Yan Wu, Mengmeng Yao, Zhuo Chen, Qianbin Li

{"title":"The other side of the coin: protein deubiquitination by Ubiquitin-Specific Protease 1 in cancer progression and therapy.","authors":"Xinlan Hu, Yan Wu, Mengmeng Yao, Zhuo Chen, Qianbin Li","doi":"10.1080/17568919.2025.2453414","DOIUrl":"10.1080/17568919.2025.2453414","url":null,"abstract":"Reversible protein ubiquitination is a crucial factor in cellular homeostasis, with Ubiquitin-Specific Protease 1 (USP1) serving as a key deubiquitinase involved in DNA damage response (DDR) and repair mechanisms in cancer. While ubiquitin ligases have been extensively studied, research on the reverse process of ubiquitination, particularly the mechanisms involving USP1, remains relatively limited. USP1 is overexpressed in various cancers, influencing tumor initiation and progression by regulating multiple associated proteins. Inhibiting USP1 effectively suppresses tumor proliferation and migration and may help overcome resistance to cisplatin and PARP inhibitors. As a potential synthetic lethal target, USP1 demonstrates significant research potential. This review highlights the biological mechanisms of USP1 in cancer progression, the signaling pathways it regulates, and the latest advancements in USP1 inhibitors, while also analyzing the opportunities and challenges of targeting USP1. By adopting the perspective of \"the other side of the coin,\" this review aims to underscore the crucial yet often overlooked role of the deubiquitinase USP1, contrasting it with the extensively studied ubiquitin ligases, and emphasizing its therapeutic potential in cancer treatment.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"329-345"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003277","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

Copper(II) complexes of 2-hydroxy-1-naphthaldehyde Schiff bases: synthesis, in vitro activity and computational studies. 2-羟基-1-萘醛席夫碱铜（II）配合物：合成、体外活性和计算研究。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI: 10.1080/17568919.2025.2458452

Tanzeela Ahmad Shah, Aftab Alam, Zainab, Majid Khan, Ahmed A Elhenawy, Amalina Mohd Tajuddin, Muhammad Ayaz, Muhammad Said, Syed Adnan Ali Shah, Ajmal Khan, Abdul Latif, Mumtaz Ali, Ahmed Al-Harrasi, Manzoor Ahmad

{"title":"Copper(II) complexes of 2-hydroxy-1-naphthaldehyde Schiff bases: synthesis, in vitro activity and computational studies.","authors":"Tanzeela Ahmad Shah, Aftab Alam, Zainab, Majid Khan, Ahmed A Elhenawy, Amalina Mohd Tajuddin, Muhammad Ayaz, Muhammad Said, Syed Adnan Ali Shah, Ajmal Khan, Abdul Latif, Mumtaz Ali, Ahmed Al-Harrasi, Manzoor Ahmad","doi":"10.1080/17568919.2025.2458452","DOIUrl":"10.1080/17568919.2025.2458452","url":null,"abstract":"Background: Due to the divers biological applications of Cu(II) complexes, we in this study reports the various Cu(II) complexes. The study aims to synthesize and assess new Cu(II) complexes as powerful β-glucuronidase inhibitors.Methods: Five Schiff base ligands and their complexes were synthesized, characterized, and screened against β-glucuronidase inhibitory activity.Results: In the series, compounds 3e, 3c, 2b, and 2c ascribed powerful inhibition ranging from (IC50 = 3.0 ± 0.7 µM) to (IC50 = 19.2 ± 0.8 µM). A precise and particular arrangement of atoms is suggested by the triclinic p-1 space group and the existence of a single molecule in an asymmetric unit, which are indispensable for the reactivity as well as the stability of the compounds. The analysis of the Hirshfeld surface provides information about the hydrogen intermolecular and π-π interactions. Based on molecular docking, binding potency increasing by complexation 3a-e compared to ligands 2a-e as well as reference Saccharic acid and uronic isofagomine inhibitor, suggesting that it may be a potent inhibitor of these receptors.Conclusion: The work recognizes latent active compounds for novel β-glucoronidase inhibitors, by further support these may be harnessed for the development of potent drugs.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"313-328"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064679","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

Dual VEGFR-2 and EGFR^T790M inhibitors of phenyldiazenes: anticancer evaluations, ADMET, docking, design and synthesis. 双VEGFR-2和EGFRT790M苯二氮的抑制剂：抗癌评价，ADMET，对接，设计和合成。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-17 DOI: 10.1080/17568919.2025.2453409

Marwa Alsulaimany, Ahmed K B Aljohani, Nour E A Abd El-Sattar, Sara A Almadani, Omar M Alatawi, Hussam Y Alharbi, Majed S Aljohani, Adel H Al-Shareef, Read Alghamdi, Saeed M Tayeb, Doaa E Keshek, Khaled El-Adl, Kurls E Anwer

{"title":"Dual VEGFR-2 and EGFRT790M inhibitors of phenyldiazenes: anticancer evaluations, ADMET, docking, design and synthesis.","authors":"Marwa Alsulaimany, Ahmed K B Aljohani, Nour E A Abd El-Sattar, Sara A Almadani, Omar M Alatawi, Hussam Y Alharbi, Majed S Aljohani, Adel H Al-Shareef, Read Alghamdi, Saeed M Tayeb, Doaa E Keshek, Khaled El-Adl, Kurls E Anwer","doi":"10.1080/17568919.2025.2453409","DOIUrl":"10.1080/17568919.2025.2453409","url":null,"abstract":"Aim: New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized.Methods & results: Cytotoxicity of our derivatives was estimated on four cancer and VERO normal cell lines targeting EGFRT790M (epidermal growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) enzymes. Our new derivatives selectively inhibited both VEGFR-2 and EGFR as they have the essential structural requirements for inhibitors of both receptors. Derivative 14 was the most active on A549, HCT116, HepG2, and MCF-7 cancers with half-maximal inhibitory concentration (IC50) = 5.50, 9.77, 7.12, and 7.85 µM respectively. The assessed derivatives 5, 7, 8, 9, 10, 12 and 14 showed IC50 = 54.40-62.60 μM against normal VERO (normal kidney) cells with low toxicity. In addition, derivatives 14, 8, 10, 7 and 9 were discovered to be very good active inhibitors of VEGFR-2 at IC50 values of 1.15, 1.35, 140, 1.78 and 1.90 µM, respectively. Furthermore, derivatives 14, 10, 8, and 9 strongly repressed EGFRT790M with IC50 = 0.28, 0.33, 0.35, and 0.50 µM correspondingly. Additionally, the highly active compounds 8, 10, and 14 showed good ADMET profile.Conclusion: Our derivatives could be considered as anticancer agents with dual VEGFR-2 and EGFRT790M inhibition.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"287-300"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003317","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

Advances of deep Neural Networks (DNNs) in the development of peptide drugs. 深度神经网络（DNN）在多肽药物开发中的应用进展。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-02-12 DOI: 10.1080/17568919.2025.2463319

Yuzhen Niu, Pingyang Qin, Ping Lin

{"title":"Advances of deep Neural Networks (DNNs) in the development of peptide drugs.","authors":"Yuzhen Niu, Pingyang Qin, Ping Lin","doi":"10.1080/17568919.2025.2463319","DOIUrl":"10.1080/17568919.2025.2463319","url":null,"abstract":"Peptides are able to bind to difficult disease targets with high potency and specificity, providing great opportunities to meet unmet medical requirements. Nevertheless, the unique features of peptides, such as their small size, high structural flexibility, and scarce data availability, bring extra challenges to the design process. Firstly, this review sums up the application of peptide drugs in treating diseases. Then, the review probes into the advantages of Deep Neural Networks (DNNs) in predicting and designing peptide structures. DNNs have demonstrated remarkable capabilities in structural prediction, enabling accurate three-dimensional modeling of peptide drugs through models like AlphaFold and its successors. Finally, the review deliberates on the challenges and coping strategies of DNNs in the development of peptide drugs, along with future research directions. Future research directions focus on further improving the accuracy and efficiency of DNN-based peptide drug design, exploring novel applications of peptide drugs, and accelerating their clinical translation. With continuous advancements in technology and data accumulation, DNNs are poised to play an increasingly crucial role in the field of peptide drug development.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"485-499"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398325","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

Camptothecin: a key building block in the design of anti-tumor agents. 喜树碱：抗肿瘤药物设计的关键组成部分。

IF 3.2 4区医学

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-25 DOI: 10.1080/17568919.2025.2458455

Bowen Liu, Lei Yao

引用次数: 0