作为微管蛋白聚合抑制剂的新型吲哚基苯基噻唑-2,4-二氢吡唑酮:多组分合成、细胞毒性评估和硅学研究。

IF 3.6 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2024-11-10 DOI:10.1002/cmdc.202400817
Bulti Bakchi, Geetanjali Devabattula, Sarvan Maddipatla, Anuradha Singampalli, Dileep Kumar Porna, Srinivas Nanduri, Anamika Sharma, Chandraiah Godugu, Venkata Madhavi Yaddanapudi
{"title":"作为微管蛋白聚合抑制剂的新型吲哚基苯基噻唑-2,4-二氢吡唑酮:多组分合成、细胞毒性评估和硅学研究。","authors":"Bulti Bakchi, Geetanjali Devabattula, Sarvan Maddipatla, Anuradha Singampalli, Dileep Kumar Porna, Srinivas Nanduri, Anamika Sharma, Chandraiah Godugu, Venkata Madhavi Yaddanapudi","doi":"10.1002/cmdc.202400817","DOIUrl":null,"url":null,"abstract":"<p><p>A facile multicomponent synthesis of new indole-based phenylthiazolyl-dihydropyrazolone hybrids, their structural characterization, biological evaluation, and in silico investigations as anticancer agents are reported. Lead molecule 5i of the series showed potent activity against MCF-7 breast cancer cells with an IC50 of 3.92 ± 0.01 µM while showing minimal toxicity to normal human lung cells (IC50 = 69.85 ± 3.95 µM). Further studies show that the compound exhibits antiproliferative activity by inducing apoptosis in MCF-7 cancer cells. The wound healing assay indicated impaired cell migration under the concentration-dependent dosage. The lead molecule 5i also successfully inhibited the tubulin polymerase enzyme with an IC50 of 4.16 ± 0.18 µM. A flow cytometric assay indicated compound 5i induced apoptosis through G0 phase cell cycle arrest. The binding mode and interactions of the compound with the tubulin were predicted by molecular modelling and calculating binding free energies. These findings explain the current series as a new class of microtubule polymerization inhibitors with anticancer activity suitable for developing anticancer agents targeting tubulin.</p>","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400817"},"PeriodicalIF":3.6000,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"New Indole-based Phenylthiazolyl-2,4-dihydropyrazolones as Tubulin polymerization inhibitors: Multicomponent synthesis, cytotoxicity evaluation, and in silico studies.\",\"authors\":\"Bulti Bakchi, Geetanjali Devabattula, Sarvan Maddipatla, Anuradha Singampalli, Dileep Kumar Porna, Srinivas Nanduri, Anamika Sharma, Chandraiah Godugu, Venkata Madhavi Yaddanapudi\",\"doi\":\"10.1002/cmdc.202400817\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>A facile multicomponent synthesis of new indole-based phenylthiazolyl-dihydropyrazolone hybrids, their structural characterization, biological evaluation, and in silico investigations as anticancer agents are reported. Lead molecule 5i of the series showed potent activity against MCF-7 breast cancer cells with an IC50 of 3.92 ± 0.01 µM while showing minimal toxicity to normal human lung cells (IC50 = 69.85 ± 3.95 µM). Further studies show that the compound exhibits antiproliferative activity by inducing apoptosis in MCF-7 cancer cells. The wound healing assay indicated impaired cell migration under the concentration-dependent dosage. The lead molecule 5i also successfully inhibited the tubulin polymerase enzyme with an IC50 of 4.16 ± 0.18 µM. A flow cytometric assay indicated compound 5i induced apoptosis through G0 phase cell cycle arrest. The binding mode and interactions of the compound with the tubulin were predicted by molecular modelling and calculating binding free energies. These findings explain the current series as a new class of microtubule polymerization inhibitors with anticancer activity suitable for developing anticancer agents targeting tubulin.</p>\",\"PeriodicalId\":147,\"journal\":{\"name\":\"ChemMedChem\",\"volume\":\" \",\"pages\":\"e202400817\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-11-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ChemMedChem\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/cmdc.202400817\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemMedChem","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cmdc.202400817","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

摘要

报告了新的吲哚基苯基噻唑基二氢吡唑啉酮杂交化合物的简便多组分合成、结构表征、生物学评价以及作为抗癌剂的硅学研究。该系列的先导分子 5i 对 MCF-7 乳腺癌细胞具有强效活性,IC50 为 3.92 ± 0.01 µM,同时对正常人肺细胞的毒性极小(IC50 = 69.85 ± 3.95 µM)。进一步的研究表明,该化合物通过诱导 MCF-7 癌细胞凋亡而表现出抗增殖活性。伤口愈合试验表明,在浓度依赖性剂量下,细胞迁移能力受损。先导分子 5i 还成功抑制了管蛋白聚合酶,其 IC50 为 4.16 ± 0.18 µM。流式细胞分析表明,化合物 5i 可通过 G0 期细胞周期停滞诱导细胞凋亡。通过分子建模和计算结合自由能,预测了化合物与微管蛋白的结合模式和相互作用。这些发现说明,目前的系列化合物是一类具有抗癌活性的新型微管聚合抑制剂,适合开发以微管蛋白为靶点的抗癌药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
New Indole-based Phenylthiazolyl-2,4-dihydropyrazolones as Tubulin polymerization inhibitors: Multicomponent synthesis, cytotoxicity evaluation, and in silico studies.

A facile multicomponent synthesis of new indole-based phenylthiazolyl-dihydropyrazolone hybrids, their structural characterization, biological evaluation, and in silico investigations as anticancer agents are reported. Lead molecule 5i of the series showed potent activity against MCF-7 breast cancer cells with an IC50 of 3.92 ± 0.01 µM while showing minimal toxicity to normal human lung cells (IC50 = 69.85 ± 3.95 µM). Further studies show that the compound exhibits antiproliferative activity by inducing apoptosis in MCF-7 cancer cells. The wound healing assay indicated impaired cell migration under the concentration-dependent dosage. The lead molecule 5i also successfully inhibited the tubulin polymerase enzyme with an IC50 of 4.16 ± 0.18 µM. A flow cytometric assay indicated compound 5i induced apoptosis through G0 phase cell cycle arrest. The binding mode and interactions of the compound with the tubulin were predicted by molecular modelling and calculating binding free energies. These findings explain the current series as a new class of microtubule polymerization inhibitors with anticancer activity suitable for developing anticancer agents targeting tubulin.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信