Pyrazolyl-s-triazine with indole motif as a novel of epidermal growth factor receptor/cyclin-dependent kinase 2 dual inhibitors

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 IC50 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 IC50 of 2.66 ± 0.26 μM and 3.78 ± 0.55 μM, respectively. Interestingly, 3i showed potent EGFR inhibition, with an IC50 of 34.1 nM compared to Erlotinib (IC50 = 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.

New spiro-indeno[1,2- b ]quinoxalines clubbed with benzimidazole scaffold as CDK2 inhibitors for halting non-small cell lung cancer; stereoselective synthesis, molecular dynamics and structural insights

“…CDK2 luminescence kinase Assay kit (Catalog #79599, Kinase-Glo Plus, Promega, USA) was used to evaluate the inhibitory potency of compound 6b using serial dilutions of 0.01–10 μM against the CDK2 inhbition. The autophosphorylation percentage inhibition by compound 6b was calculated using the following equation: 100-[Control/Treated-Control)] using the curves of percentage inhibition of eight concentrations of each compound, IC 50 was calculated using the GraphPad prism7 software 54 , 55 .…”

Synthesis and SARs study of novel spiro‐oxindoles as potent antiproliferative agents with CDK‐2 inhibitory activities

“…)] using the curves of the percentage inhibition of eight concentrations of each compound, IC 50 was calculated using the GraphPad prism7 software. [72,73]…”

Recent biological applications of heterocyclic hybrids containing s-triazine scaffold

“…Bioconjugates of pyrazole clubbed s -triazine ( 53 ) with an addition motif of indole ring were designed and its antiproliferation activity was evaluated as a kinase inhibitor. 60 For this purpose, the inhibitory effect was evaluated against two enzymes, EGFR and CDK. The cytotoxicity of conjugates was also evaluated against three different cancer cell-lines and results were obtained to be A549 = 2.40 ± 0.64 μM, MCF-7 = 3.28 ± 0.16 μM, HDFs = 3.78 ± 0.55 μM, EGFR = 34.1 ± 1.58 nM, and CDK-2 = 108.3 ± 3.12 nM for the most prominent conjugate.…”