In:
Frontiers in Chemistry, Frontiers Media SA, Vol. 10 ( 2022-11-25)
Abstract:
A series of pyrazolyl- s -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 3h , 3i , and 3j showed promising cytotoxic activity against two cancer cell lines, namely A549, MCF-7, and HDFs (non-cancerous human dermal fibroblasts). Compound 3j was the most active candidate against A549, with an IC 50 of 2.32 ± 0.21 μM. Compounds 3h and 3i were found to be the most active hybrids against MCF-7 and HDFs, with an IC 50 of 2.66 ± 0.26 μM and 3.78 ± 0.55 μM, respectively. Interestingly, 3i showed potent EGFR inhibition, with an IC 50 of 34.1 nM compared to Erlotinib (IC 50 = 67.3 nM). At 10 μM, this candidate caused 93.6% and 91.4% of EGFR and CDK-2 inhibition, respectively. Furthermore, 3i enhanced total lung cancer cell apoptosis 71.6-fold (43.7% compared to 0.61% for the control). Given the potent cytotoxicity exerted by 3i through apoptosis-mediated activity, this compound emerges as a promising target-oriented anticancer agent.
Type of Medium:
Online Resource
ISSN:
2296-2646
DOI:
10.3389/fchem.2022.1078163
DOI:
10.3389/fchem.2022.1078163.s001
DOI:
10.3389/fchem.2022.1078163.s002
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2711776-5
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