Design, synthesis, anticancer activity and docking studies of novel quinazoline-based thiazole derivatives as EGFR kinase inhibitors

M S Raghu; H A Swarup; T Shamala; B S Prathibha; K Yogesh Kumar; Fahd Alharethy; M K Prashanth; Byong-Hun Jeon

doi:10.1016/j.heliyon.2023.e20300

Design, synthesis, anticancer activity and docking studies of novel quinazoline-based thiazole derivatives as EGFR kinase inhibitors

Heliyon. 2023 Sep 20;9(9):e20300. doi: 10.1016/j.heliyon.2023.e20300. eCollection 2023 Sep.

Authors

M S Raghu¹, H A Swarup², T Shamala², B S Prathibha², K Yogesh Kumar³, Fahd Alharethy⁴, M K Prashanth², Byong-Hun Jeon⁵

Affiliations

¹ Department of Chemistry, New Horizon College of Engineering, Bengaluru, 560 103, India.
² Department of Chemistry, B N M Institute of Technology, Bengaluru, 560 070, India.
³ Department of Chemistry, Faculty of Engineering and Technology, Jain University, Ramanagara, 562 112, India.
⁴ Department of Chemistry, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
⁵ Department of Earth Resources and Environmental Engineering, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Abstract

The in vitro anticancer efficacy of a new series of quinazoline-based thiazole derivatives was explored. Three cancer cell lines, MCF-7, HepG2, and A548, as well as the normal Vero cell lines, were tested employing the synthesized quinazoline-based thiazole compounds (4a-j). All of these compounds showed a moderate to significant cytotoxic impact that would have been noticeable and, in some cases, much more pronounced than the widely used drug erlotinib. For the MCF-7, HepG2, and A549 cell lines, respectively, the IC₅₀ values of compound 4i were 2.86, 5.91, and 14.79 μM while those of compound 4j were 3.09, 6.87, and 17.92 μM. For their in vitro inhibitory effects against different EGFR kinases, such as the wild-type, L858R/T790 M, and L858R/T790 M/C797S, all the synthesized compounds were tested. The IC₅₀ values for compound 4f against the wild-type, L858R/T790 M, and L858R/T790 M/C797S mutant EGFR kinases were 2.17, 2.81, and 3.62 nM, respectively. Investigations on the molecular docking of significant molecules indicated potential mechanisms of binding into the EGFR kinase active sites. By using in-silico simulations, compounds' putative drug-like qualities were verified. Finally, it has been shown that the newly synthesized compounds 4i and 4j are good candidates and beneficial for future design, optimization, and research to build more potent and selective EGFR kinase inhibitors with higher anticancer activity.

Keywords: Anticancer; EGFR; Molecular docking; Quinazoline; Thiazole.