Design, synthesis, and antiproliferative activity of new indole/1,2,4-triazole/chalcone hybrids as EGFR and/or c-MET inhibitors.

Autor: Mahmoud E; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia, Egypt., Abdelhamid D; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.; Raabe College of Pharmacy, Ohio Northern University, Ohio, USA., Youssif BGM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt., Gomaa HAM; Pharmacology Department, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia., Hayallah AM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sphinx University, New-Assiut, Egypt., Abdel-Aziz M; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Sep; Vol. 357 (9), pp. e2300562. Date of Electronic Publication: 2024 Jun 21.
DOI: 10.1002/ardp.202300562
Abstrakt: A novel group of indolyl-1,2,4-triazole-chalcone hybrids was designed, synthesized, and assessed for their anticancer activity. The synthesized compounds exhibited significant antiproliferative activity. Compounds 9a and 9e exhibited significant cancer inhibition with GI 50 ranging from 3.69 to 20.40 µM and from 0.29 to >100 µM, respectively. Both compounds displayed a broad spectrum of anticancer activity with selectivity ratios ranging between 0.50-2.78 and 0.25-2.81 at the GI 50 level, respectively. The synthesized compounds were also screened for their cytotoxicity by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazol (MTT) assay and for inhibition of epidermal growth factor receptor (EGFR) and c-MET (mesenchymal-epithelial transition factor). Some of the tested compounds exhibited significant inhibition against EGFR and/or c-MET. Compound 9b showed the highest c-MET inhibition (IC 50  = 4.70 nM) compared to foretinib (IC 50  = 2.5 nM). Compound 9d showed equipotent activity compared with erlotinib against EGFR (IC 50  = 0.052 µM) and displayed significant c-MET inhibition with an IC 50 value of 4.90 nM.
(© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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