Monica Chauhan, Chintu Prajapati, Sadaf Mirza, Rahul Barot, Rasana Yadav, Mahesh Barmade, Dhruvi Kakadiya, Ravi Vijayvargia, Bijaya Haobam, Anurag Tk Baidya, Rajnish Kumar, M R Yadav, Prashant Murumkar
{"title":"作为抗结核药物的一些新型 3-苯基吡唑并[1,5-a]嘧啶-2,7(1H,4H)-二酮化合物的设计、合成、生物学评价和分子动力学。","authors":"Monica Chauhan, Chintu Prajapati, Sadaf Mirza, Rahul Barot, Rasana Yadav, Mahesh Barmade, Dhruvi Kakadiya, Ravi Vijayvargia, Bijaya Haobam, Anurag Tk Baidya, Rajnish Kumar, M R Yadav, Prashant Murumkar","doi":"10.1080/07391102.2023.2249109","DOIUrl":null,"url":null,"abstract":"<p><p>Decaprenylphosphoryl-β-d-ribose-2'-epimerase (DprE1) is a druggable target which is being exploited for the development of new anti-TB agents. In the present work, we report developing a pharmacophore model and performing virtual screening of Asinex database using the developed pharmacophore model to get eight hits as potential DprE1 inhibitors. The hits were used as leads to design new 3-phenylpyrazolo[1,5-<i>a</i>]pyrimidine-2,7(1<i>H</i>,4<i>H</i>)-dione based potential anti-TB agents. On the basis of the identified lead molecules, a total of 18 compounds were synthesized and evaluated for their anti-TB activity by using MABA. ADMET predictions for all the compounds revealed that these compounds have drug-like and lead-like properties. One of the final compounds was found to exhibit potent anti-TB activity against <i>Mycobacterium bovis</i>.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis, biological evaluation and molecular dynamics of some novel 3-phenylpyrazolo[1,5-<i>a</i>]pyrimidine-2,7(1<i>H</i>,4<i>H</i>)-dione based compounds as anti-tubercular agents.\",\"authors\":\"Monica Chauhan, Chintu Prajapati, Sadaf Mirza, Rahul Barot, Rasana Yadav, Mahesh Barmade, Dhruvi Kakadiya, Ravi Vijayvargia, Bijaya Haobam, Anurag Tk Baidya, Rajnish Kumar, M R Yadav, Prashant Murumkar\",\"doi\":\"10.1080/07391102.2023.2249109\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Decaprenylphosphoryl-β-d-ribose-2'-epimerase (DprE1) is a druggable target which is being exploited for the development of new anti-TB agents. In the present work, we report developing a pharmacophore model and performing virtual screening of Asinex database using the developed pharmacophore model to get eight hits as potential DprE1 inhibitors. The hits were used as leads to design new 3-phenylpyrazolo[1,5-<i>a</i>]pyrimidine-2,7(1<i>H</i>,4<i>H</i>)-dione based potential anti-TB agents. On the basis of the identified lead molecules, a total of 18 compounds were synthesized and evaluated for their anti-TB activity by using MABA. ADMET predictions for all the compounds revealed that these compounds have drug-like and lead-like properties. One of the final compounds was found to exhibit potent anti-TB activity against <i>Mycobacterium bovis</i>.Communicated by Ramaswamy H. Sarma.</p>\",\"PeriodicalId\":15272,\"journal\":{\"name\":\"Journal of Biomolecular Structure & Dynamics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biomolecular Structure & Dynamics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/07391102.2023.2249109\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomolecular Structure & Dynamics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/07391102.2023.2249109","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/1 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Design, synthesis, biological evaluation and molecular dynamics of some novel 3-phenylpyrazolo[1,5-a]pyrimidine-2,7(1H,4H)-dione based compounds as anti-tubercular agents.
Decaprenylphosphoryl-β-d-ribose-2'-epimerase (DprE1) is a druggable target which is being exploited for the development of new anti-TB agents. In the present work, we report developing a pharmacophore model and performing virtual screening of Asinex database using the developed pharmacophore model to get eight hits as potential DprE1 inhibitors. The hits were used as leads to design new 3-phenylpyrazolo[1,5-a]pyrimidine-2,7(1H,4H)-dione based potential anti-TB agents. On the basis of the identified lead molecules, a total of 18 compounds were synthesized and evaluated for their anti-TB activity by using MABA. ADMET predictions for all the compounds revealed that these compounds have drug-like and lead-like properties. One of the final compounds was found to exhibit potent anti-TB activity against Mycobacterium bovis.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.