Synthesis and molecular docking of hybrids ionic azole Schiff bases as novel CDK1 inhibitors and anti-breast cancer agents: In vitro and in vivo study

Abstract

Three new hybrid ionic vanillyl-azole-Schiff bases (IVASBs) have synthesized and their antitumor performances were assessed in vitro against MCF-7 cells and in vivo against Ehrlich solid tumor (EST). The high binding energy score of IVASB3‒CDK1 (−3.43 kcal/mol) makes IVASB3 the most potent anti-breast cancer candidate (IC50 3.73 ± 0.2 µg/mL). Cell cycle analysis showed that IVASB3 was significantly increased the percent of EST cells undergoing the sub G1 phase and decreased the percent of cells in the S phase. In addition, the administration of IVASB1, IVASB2, and IVASB3 to tumorized mice caused a significant reduction in cyclin-dependent kinase-1 (CDK1) expression by 41.27%, 53.31%, and 78.57%, respectively. Moreover, concentrations of poly ADP-ribose polymerase (PARP) and vascular endothelial growth factor (VEGF) significantly decreased in the serum of tumorized mice which received IVASBs. Consequently, the antitumor effects of IVASBs could be attributed to their capacity to diminish CDK1, PAPR, and VEGF expressions.