Pub Date : 2024-09-11DOI: 10.1080/14756366.2024.2386668
Mai S. El-Shoukrofy, Amal Atta, Salwa Fahmy, Dharmarajan Sriram, Michael G. Shehat, Ibrahim M. Labouta, Mona A. Mahran
New Biginelli adducts were rationalised, via the introduction of selected anti-tubercular (TB) pharmacophores into the dihydropyrimidine (DHPM) ring of deoxythymidine monophosphate (dTMP), the natu...
通过在单磷酸脱氧胸苷（dTMP）的二氢嘧啶（DHPM）环（天然...
{"title":"Challenging the Biginelli scaffold to surpass the first line antitubercular drugs: Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibition activity and molecular modelling studies","authors":"Mai S. El-Shoukrofy, Amal Atta, Salwa Fahmy, Dharmarajan Sriram, Michael G. Shehat, Ibrahim M. Labouta, Mona A. Mahran","doi":"10.1080/14756366.2024.2386668","DOIUrl":"https://doi.org/10.1080/14756366.2024.2386668","url":null,"abstract":"New Biginelli adducts were rationalised, via the introduction of selected anti-tubercular (TB) pharmacophores into the dihydropyrimidine (DHPM) ring of deoxythymidine monophosphate (dTMP), the natu...","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"60 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1080/14756366.2024.2390911
Jinhao Liang,Jin Huang,Jianzhan Yang,Weihong Liang,Haoxiang Li,Yunshan Wu,Bo Liu
Rho family GTPases regulate cellular processes and promote tumour growth and metastasis; thus, RhoA is a potential target for tumour metastasis inhibition. However, limited progress has been made in the development of RhoA targeting anticancer drugs. Here, we synthesised benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives based on a covalent inhibitor of RhoA (DC-Rhoin), reported in our previous studies. The observed structure-activity relationship (contributed by carboxamide in C-3 and 1-methyl-1H-pyrazol in C-5) enhanced the anti-proliferative activity of the derivatives. Compound b19 significantly inhibited the proliferation, migration, and invasion of MDA-MB-231 cells and promoted their apoptosis. The suppression of myosin light chain phosphorylation and the formation of stress fibres confirmed the inhibitory activity of b19 via the RhoA/ROCK pathway. b19 exhibited a different binding pattern from DC-Rhoin, as observed in molecular docking analysis. This study provides a reference for the development of anticancer agents targeting the RhoA/ROCK pathway.
{"title":"Synthesis and in vitro evaluation of benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives as anticancer agents targeting the RhoA/ROCK pathway.","authors":"Jinhao Liang,Jin Huang,Jianzhan Yang,Weihong Liang,Haoxiang Li,Yunshan Wu,Bo Liu","doi":"10.1080/14756366.2024.2390911","DOIUrl":"https://doi.org/10.1080/14756366.2024.2390911","url":null,"abstract":"Rho family GTPases regulate cellular processes and promote tumour growth and metastasis; thus, RhoA is a potential target for tumour metastasis inhibition. However, limited progress has been made in the development of RhoA targeting anticancer drugs. Here, we synthesised benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives based on a covalent inhibitor of RhoA (DC-Rhoin), reported in our previous studies. The observed structure-activity relationship (contributed by carboxamide in C-3 and 1-methyl-1H-pyrazol in C-5) enhanced the anti-proliferative activity of the derivatives. Compound b19 significantly inhibited the proliferation, migration, and invasion of MDA-MB-231 cells and promoted their apoptosis. The suppression of myosin light chain phosphorylation and the formation of stress fibres confirmed the inhibitory activity of b19 via the RhoA/ROCK pathway. b19 exhibited a different binding pattern from DC-Rhoin, as observed in molecular docking analysis. This study provides a reference for the development of anticancer agents targeting the RhoA/ROCK pathway.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"26 1","pages":"2390911"},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.1080/14756366.2024.2343350
Jihyung Kim, Chang Gyun Im, Kyujin Oh, Ji Min Lee, Fatimah Al-Rubaye, K. Min
Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c, with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments.
{"title":"Discovery of novel FGFR4 inhibitors through a build-up fragment strategy","authors":"Jihyung Kim, Chang Gyun Im, Kyujin Oh, Ji Min Lee, Fatimah Al-Rubaye, K. Min","doi":"10.1080/14756366.2024.2343350","DOIUrl":"https://doi.org/10.1080/14756366.2024.2343350","url":null,"abstract":"Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c, with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"111 8","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140659191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1080/14756366.2024.2330907
Maria Galvez-Llompart, Jesús Hierrezuelo, Mariluz Blasco, Riccardo Zanni, Jorge Galvez, A. de Vicente, A. Pérez-García, D. Romero
Abstract Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure–activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (−) antibacterial, and biofilm formation inhibition activity. The models were applied to the virtual screening of a commercial chemical database, resulting in the selection of 58 compounds. Subsequent in vitro assays showed that three of these compounds exhibited the most promising antibacterial activity, with potential applications in enhancing food and medical device safety.
摘要 抗菌药耐药性（AMR）是一个紧迫的全球性问题，抗生素的滥用和细菌生物膜的形成加剧了这一问题，导致高达 80% 的人类细菌感染。本研究提出了一种解决 AMR 问题的计算策略，即基于分子拓扑学开发三种新型定量结构-活性关系 (QSAR) 模型，以确定潜在的抗生物膜和抗菌剂。这些模型旨在确定革兰氏（+）抗菌、革兰氏（-）抗菌和抑制生物膜形成活性的化学拓扑模式。这些模型被应用于商业化学数据库的虚拟筛选，最终选出了 58 种化合物。随后的体外试验表明，其中三种化合物具有最有前途的抗菌活性，可用于提高食品和医疗器械的安全性。
{"title":"Targeting bacterial growth in biofilm conditions: rational design of novel inhibitors to mitigate clinical and food contamination using QSAR","authors":"Maria Galvez-Llompart, Jesús Hierrezuelo, Mariluz Blasco, Riccardo Zanni, Jorge Galvez, A. de Vicente, A. Pérez-García, D. Romero","doi":"10.1080/14756366.2024.2330907","DOIUrl":"https://doi.org/10.1080/14756366.2024.2330907","url":null,"abstract":"Abstract Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure–activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (−) antibacterial, and biofilm formation inhibition activity. The models were applied to the virtual screening of a commercial chemical database, resulting in the selection of 58 compounds. Subsequent in vitro assays showed that three of these compounds exhibited the most promising antibacterial activity, with potential applications in enhancing food and medical device safety.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"119 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140669496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertak...
{"title":"Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells","authors":"Loredana Salerno, Antonietta Notaro, Valeria Consoli, Federica Affranchi, Valeria Pittalà, Valeria Sorrenti, Luca Vanella, Michela Giuliano, Sebastiano Intagliata","doi":"10.1080/14756366.2024.2337191","DOIUrl":"https://doi.org/10.1080/14756366.2024.2337191","url":null,"abstract":"Colon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertak...","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"57 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A novel series of hydantoins incorporating phthalimides has been synthesised by condensation of activated phthalimides with 1-aminohydantoin and investigated for their inhibitory activity against a...
{"title":"Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids","authors":"Morteza Abdoli, Alessandro Bonardi, Paola Gratteri, Claudiu T. Supuran, Raivis Žalubovskis","doi":"10.1080/14756366.2024.2335927","DOIUrl":"https://doi.org/10.1080/14756366.2024.2335927","url":null,"abstract":"A novel series of hydantoins incorporating phthalimides has been synthesised by condensation of activated phthalimides with 1-aminohydantoin and investigated for their inhibitory activity against a...","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"198 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-22DOI: 10.1080/14756366.2024.2314233
Xin Gan, Yuna Wu, Min Zhu, Bo Liu, Miaomiao Kong, Zixuan Xi, Ke Li, Haibao Wang, Tiande Su, Jiali Yao, Fatehi Khushafah, Baozhu Yi, Jiabing Wang, Wulan Li, Jianzhang Wu
The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and les...
{"title":"Design, synthesis, and evaluation of cyclic C7-bridged monocarbonyl curcumin analogs containing an o-methoxy phenyl group as potential agents against gastric cancer","authors":"Xin Gan, Yuna Wu, Min Zhu, Bo Liu, Miaomiao Kong, Zixuan Xi, Ke Li, Haibao Wang, Tiande Su, Jiali Yao, Fatehi Khushafah, Baozhu Yi, Jiabing Wang, Wulan Li, Jianzhang Wu","doi":"10.1080/14756366.2024.2314233","DOIUrl":"https://doi.org/10.1080/14756366.2024.2314233","url":null,"abstract":"The structure-activity relationship (SAR) between toxicity and the types of linking ketones of C7 bridged monocarbonyl curcumin analogs (MCAs) was not clear yet. In the pursuit of effective and les...","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"53 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-13DOI: 10.1080/14756366.2023.2290910
Karol Biernacki, Olga Ciupak, Mateusz Daśko, Janusz Rachon, Damian Flis, Justyna Budka, Iwona Inkielewicz-Stępniak, Anna Czaja, Janusz Rak, Sebastian Demkowicz
In the present work, we report a new series of potent SARS-CoV-2 Main Protease (Mpro) inhibitors based on maleimide derivatives. The inhibitory activities were tested in an enzymatic assay using re...
{"title":"Development of potent and effective SARS-CoV-2 main protease inhibitors based on maleimide analogs for the potential treatment of COVID-19","authors":"Karol Biernacki, Olga Ciupak, Mateusz Daśko, Janusz Rachon, Damian Flis, Justyna Budka, Iwona Inkielewicz-Stępniak, Anna Czaja, Janusz Rak, Sebastian Demkowicz","doi":"10.1080/14756366.2023.2290910","DOIUrl":"https://doi.org/10.1080/14756366.2023.2290910","url":null,"abstract":"In the present work, we report a new series of potent SARS-CoV-2 Main Protease (Mpro) inhibitors based on maleimide derivatives. The inhibitory activities were tested in an enzymatic assay using re...","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"59 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-12DOI: 10.1080/14756366.2023.2292482
Shaza H. Aly, Ahmed M. Elissawy, Mahmoud A. El Hassab, Taghreed A. Majrashi, Fatma E. Hassan, Eslam B. Elkaeed, Wagdy M. Eldehna, Abdel Nasser B. Singab
This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The result...
{"title":"Comparative metabolic study of the chloroform fraction of three Cystoseira species based on UPLC/ESI/MS analysis and biological activities","authors":"Shaza H. Aly, Ahmed M. Elissawy, Mahmoud A. El Hassab, Taghreed A. Majrashi, Fatma E. Hassan, Eslam B. Elkaeed, Wagdy M. Eldehna, Abdel Nasser B. Singab","doi":"10.1080/14756366.2023.2292482","DOIUrl":"https://doi.org/10.1080/14756366.2023.2292482","url":null,"abstract":"This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The result...","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"3 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-12DOI: 10.1080/14756366.2023.2289007
Zorana Ferjancic, Filip Bihelovic, Bojan Vulovic, Radomir Matovic, Milena Trmcic, Aleksandar Jankovic, Milos Pavlovic, Filip Djurkovic, Radivoje Prodanovic, Aleksandra Djurdjevic Djelmas, Nevena Kalicanin, Mario Zlatovic, Dusan Sladic, Thomas Vallet, Marco Vignuzzi, Radomir N. Saicic
We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of...
{"title":"Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies","authors":"Zorana Ferjancic, Filip Bihelovic, Bojan Vulovic, Radomir Matovic, Milena Trmcic, Aleksandar Jankovic, Milos Pavlovic, Filip Djurkovic, Radivoje Prodanovic, Aleksandra Djurdjevic Djelmas, Nevena Kalicanin, Mario Zlatovic, Dusan Sladic, Thomas Vallet, Marco Vignuzzi, Radomir N. Saicic","doi":"10.1080/14756366.2023.2289007","DOIUrl":"https://doi.org/10.1080/14756366.2023.2289007","url":null,"abstract":"We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of...","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"36 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138689073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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