Design, Synthesis, in Silico Molecular Docking and ADMET Studies of Indole‐Sulfonamide Derivatives as Tubulin Polymerization Inhibiting Agents

Author:

Dasari Gouthami1ORCID,Thirukovela Narasimha Swamy2ORCID,Kumar Gajjela Bharath3ORCID,Bandari Srinivas2ORCID

Affiliation:

1. Department of Chemistry J.B. Institute of Engineering & Technology Yenkapally (V), Moinabad (M), Ranga Reddy (D), Hyderabad 500075 India

2. Department of Chemistry Chaitanya Deemed to be University Himayathnagar, Moinabad, Hyderabad, Telangana 500075 India

3. Department of Pharmacological Sciences Icahn School of Medicine at Mount Sinai Icahn Building, Room 16–50 A, 1425 Madison Aven, Manhattan New York NK-10029 USA

Abstract

AbstractIn this paper, we describe the synthesis of indolyl aryl sulfonamide conjugates (6 an). The anti‐tumour activity was assessed on three human cancer cell lines: A‐549 (lung), HeLa (cervix), and MCF‐7 (breast). Nocodazole was used as a standard drug by employing the MTT assay method. The results show that the compounds 6 b, 6 l, and 6 m have shown more potent activity as compared to the standard drug Nocodazole. In a cell survivability test (MCF‐10 A), three potent compounds (6 b, 6 l, and 6 m) were evaluated against the normal breast cell line, although neither of them displayed any significant cytotoxicity with IC50 values greater than 78.45 μM. Furthermore, the compounds 6 b, 6 l, and 6 m were tested for tyrosine kinase EGFR inhibitory action using Combretastatin A‐4 as the reference drug. The in vitro tubulin polymerization inhibitory activity indicates that the compounds 6b and 6 l showed promising potency with IC50 values of 2.40±0.02 and 2.34±0.03 mM, respectively. In addition to this, molecular docking studies of compounds 6 b, 6 l, and 6 m demonstrated that these compounds had more EGFR binding interactions. The potent compounds 6 b, 6 l, and 6 m were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. While the compounds 6 b, 6 l, and 6 m followed five filters (Lipinski rule, Ghose rule, Veber rule, Egan rule, and Muegge rule) without any deviation.

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3