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Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with in vitro antitumor activity towards non-small lung cancer.

ABSTRACT: New series of thiazolyl-pyrazoline derivatives (7a-7d, 10a-10d and 13a-13f) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds 10b and 10d exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC50 = 40.7 ± 1.0 and 32.5 ± 2.2 nM, respectively) and VEGFR-2 (IC50 = 78.4 ± 1.5 and 43.0 ± 2.4 nM, respectively). The best anti-proliferative activity for the examined thiazolyl-pyrazolines was observed against the non-small lung cancer cells (NSCLC). Compounds 10b and 10d displayed pronounced efficacy against A549 (IC50 = 4.2 and 2.9 µM, respectively) and H441 cell lines (IC50 = 4.8 and 3.8 µM, respectively). Moreover, our results indicated that 10b and 10d were much more effective towards EGFR-mutated NSCLC cell lines (NCI-H1650 and NCI-H1975 cells) than gefitinib. Finally, compounds 10b and 10d induce G2/M cell cycle arrest and apoptosis and inhibit migration in A549 cancerous cells.

SUBMITTER: Abdelsalam EA 

PROVIDER: S-EPMC9415638 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with <i>in vitro</i> antitumor activity towards non-small lung cancer.

Abdelsalam Esraa A EA   Abd El-Hafeez Amer Ali AA   Eldehna Wagdy M WM   El Hassab Mahmoud A MA   Marzouk Hala Mohamed M HMM   Elaasser Mahmoud M MM   Abou Taleb Nageh A NA   Amin Kamilia M KM   Abdel-Aziz Hatem A HA   Ghosh Pradipta P   Hammad Sherif F SF  

Journal of enzyme inhibition and medicinal chemistry 20221201 1

New series of thiazolyl-pyrazoline derivatives (<b>7a-7d</b>, <b>10a-10d</b> and <b>13a-13f</b>) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds <b>10b</b> and <b>10d</b> exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC<sub>50</sub> = 40.7 ± 1.0 and 32.5 ± 2.2 nM, respectively) and VEGFR-2 (IC<sub>50</sub> = 78.4 ± 1.5 and 43.0 ± 2.4 nM, respectively). The best anti-proliferative activity  ...[more]

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