Pyrazolyl-s-triazine with Indole Motif As a Novel of Epidermal Growth Factor Receptor/cyclin-dependent Kinase 2 Dual Inhibitors

Overview

Journal Front Chem

Specialty Chemistry

Date 2022 Dec 12

PMID 36505739

Authors

Ihab Shawish

Mohamed S Nafie

Assem Barakat

Ali Aldalbahi

Hessa H Al-Rasheed

M Ali

Walhan Alshaer

Mazhar Al Zoubi

Samha Al Ayoubi

Beatriz G de la Torre

Fernando Albericio

Ayman El-Faham

Affiliations

Soon will be listed here.

Abstract

A series of pyrazolyl--triazine compounds with an indole motif was designed, synthesized, and evaluated for anticancer activity targeting dual EGFR and CDK-2 inhibitors. The compounds were tested for cytotoxicity using the MTT assay. Compounds , , and showed promising cytotoxic activity against two cancer cell lines, namely A549, MCF-7, and HDFs (non-cancerous human dermal fibroblasts). Compound was the most active candidate against A549, with an IC of 2.32 ± 0.21 μM. Compounds and were found to be the most active hybrids against MCF-7 and HDFs, with an IC of 2.66 ± 0.26 μM and 3.78 ± 0.55 μM, respectively. Interestingly, showed potent EGFR inhibition, with an IC of 34.1 nM compared to Erlotinib (IC = 67.3 nM). At 10 μM, this candidate caused 93.6% and 91.4% of EGFR and CDK-2 inhibition, respectively. Furthermore, enhanced total lung cancer cell apoptosis 71.6-fold (43.7% compared to 0.61% for the control). Given the potent cytotoxicity exerted by through apoptosis-mediated activity, this compound emerges as a promising target-oriented anticancer agent.

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