New quinoxaline-piperazine-oxazole conjugates: Synthesis,in vitro anticancer,in silico ADMET,and molecular docking studies

In this paper, we describe the synthesis of some new quinoxaline-piperazine-oxazole amide conjugates 6a-n from 3-chloroquinoxaline-2-carbonitrile using well-known reaction sequences. The synthesized compounds were characterized by ¹H NMR,¹³C NMR, and mass spectral analysis. The compounds were tested for their in vitro antiproliferative activity toward four different cancer cell lines such as PC-3, MCF-7, DU-145, and A-549 by MTT method. The compounds, 6c, 6h, 6i , and 6n were found to be more potent than the standard Erlotinib. In vitro tyrosine kinase EGFR inhibition studies using four potent compounds revealed that 6n has double inhibiting tendency with value IC₅₀ of 0.22 μM and 6h with value of IC₅₀ 0.27 μM compared to reference compound. Molecular docking studies of active compounds, 6c , 6h , 6i , and 6n on EGFR receptor suggested that all the compounds have more binding energies than that of Erlotinib. Furthermore, the in silico pharmacokinetic profile was accomplished for the active compounds, 6c , 6h , 6i , and 6n using SWISS/ADME and pk CSM, whereas compounds, 6h , 6i , and 6c followed Lipinski rule, Veber rule, Egan rule and Muegge rule. The remaining compound 6n did not follow Lipinski rule, Ghose rule because one common violation, that is, because of high molecular weight (MW > 350).