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Synlett 2023; 34(01): 49-56
DOI: 10.1055/s-0042-1751378
letter

Design, Synthesis and Biological Evaluation of 2-Phenylquinazolin-4-yl 4-Methylbenzenesulfonate Derivatives as Anticancer Agents via Tubulin Inhibition

Kapil Kumar Goel  ∗
a   Department of Pharmaceutical Sciences, Gurukul Kangri (Deemed to be University), Haridwar-249404, India
b   Amity Institute of Pharmacy, Amity University, Sector 125, Noida, Uttar Pradesh 201301, India
,
Satyendra Kumar Rajput
a   Department of Pharmaceutical Sciences, Gurukul Kangri (Deemed to be University), Haridwar-249404, India
,
Prince Prashant Sharma
a   Department of Pharmaceutical Sciences, Gurukul Kangri (Deemed to be University), Haridwar-249404, India
,
Monalisa Mukherjee
c   Amity Institute of Click Chemistry Research and Studies, Amity ­University, Sector 125, Noida, Uttar Pradesh 201301, India
,
Rajeev Kharb∗
b   Amity Institute of Pharmacy, Amity University, Sector 125, Noida, Uttar Pradesh 201301, India
› Author AffiliationsThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Abstract

Malignant behavior and multiple abnormal cellular functions have rendered cancer a great challenge for scientists to treat. The rising death toll presents an alarming situation, and the side effects associated with marketed drugs has further increased the quest to develop new anticancer drug molecules. We herein report a rationally designed 2,4-disubstituted quinazoline-based bioactive pharmacophore possessing different substitution patterns to obtain potent anticancer active agents targeting tubulin polymerization. In this series, two compounds showed potent cytotoxicity against all four cancer cell lines (MCF-7, MD-MBA-231, A549, and HCT-116) comparable to that of colchicine. The compounds showed cell cycle arrest in the G2/M phase and induced apoptosis, which showed these compounds might act via binding to the colchicine binding site. These results were further confirmed via tubulin polymerization inhibition, which showed a similar profile to colchicine. Compounds with a propargyl moiety showed very low cytotoxicity as compared to colchicines, even in the presence of a trimethoxy substituent at the quinazoline ring, except for compound case. Two compounds are obtained as potential lead compounds for the development of active anticancer agents, with one having a similar profile to colchicine activity on tubulin polymerization inhibition. These compounds represent promising leads that deserve further investigation and optimization.

Key words

quinazoline - anticancer compounds - apoptosis - tubulin polymerization - G2/M phase

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751378.
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Publication History

Received: 31 August 2022

Accepted after revision: 04 October 2022

Article published online:
28 October 2022

© 2022. Thieme. All rights reserved

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