Novel sulfonyl thiazolyl-hydrazone derivatives as EGFR inhibitors: Design, synthesis, biological evaluation and molecular docking studies.

Autor: Farghaly TA; Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt. Electronic address: thoraya-f@cu.edu.eg., Abbas EMH; Department of Chemistry, Natural and Microbial Products, National Research Center, Dokki, Cairo, Egypt., Al-Soliemy AM; Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, Saudi Arabia., Sabour R; Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Shaaban MR; Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, Saudi Arabia. Electronic address: rabiemohamed@hotmail.com.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2022 Apr; Vol. 121, pp. 105684. Date of Electronic Publication: 2022 Feb 15.
DOI: 10.1016/j.bioorg.2022.105684
Abstrakt: New hydrazonoyl-sulfonylthiazoles were designed and synthesized as EGFR inhibitors. The new sulfonylthiazole derivatives were assessed in vitro to measure their effect on EGFR. They revealed marked inhibitory activity against EGFR kinase having IC 50 range from 0.037 to 0.317 μM compared to reference drug dasatinib (IC 50  = 0.077 μM). Six derivatives of the newly synthesized compounds showed potent inhibitory activity relative to dasatinib. Furthermore, the new hits were examined concerning their cytotoxic effect on human breast cancer cell line (MCF7), hepatic cancer cell line (HepG2) using MTT assay. N-(2-Benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-thiazol-2-yl)-hydrazine (IC 50  = 1.24 μM) revealed higher potency than dasatinib (IC 50  = 11.6 μM) against MCF7cell line. Besides, N-(2-benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-5-p-tolylazo-thiazol-2-yl)-hydrazine exhibited excellent cytotoxicity against HepG2cell line (IC 50  = 3.61 μM), exceeding that of dasatinib (IC 50  = 14.10 μM). In addition to low cytotoxic effect on normal (WI-38) cells, describing the high safety profiles of these compounds. Moreover, molecular docking was done in order to determine the possible binding modes of such compounds inside the binding site of EGFR.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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