Molecular docking, synthesis and anticancer activity of thiosemicarbazone derivatives against MCF-7 human breast cancer cell line

The aim of this study was to synthesize and evaluate anticancer activity of 2-hydroxy benzaldehyde and 4-hydroxy benzaldehyde thiosemicarbazone (2-HBTSc and 4-HBTSc) against MCF-7 breast cancer cell line. The ligands were prepared and characterized by UV vis, IR and NMR. MTT assay was used to assess viability of cells. RNA isolation, extraction and cDNA synthesis were done. Then all groups were subjected to RT-qPCR using Gene expression specific primers. Also, western blot protein expression and molecular docking were done. Two-way ANOVA with Tukey post-hoc test was employed to test the significance using GraphPad Prism. The IC50 values were 3.36μg/ml and 3.60μg/ml for 2-HBTSc and 4-HBTSc treated MCF-7 tumor cells respectively. Tumor cell growth inhibition ranged from 38 to 49.27% in 4-HBTSc treated cells, and 19 to 25% in 2-HBTSc treated cells with increase in doses 5 μg/ml to 20 μg/ml. The protein and gene expression result showed a significant upregulation in tumor suppressor and apoptosis inducing genes while, oncogene activity was significantly downregulated. Specifically, BRCA2 and pRB gene showed the highest expression in 4-HBTSc and 2-HBTSc treated cells respectively. Conversely, RAS oncogene was downregulated significantly. Docking result showed that both 2-HBTSc and 4-HBTSc have the potential to inhibit Estrogen Receptor Alpha Ligand Binding Domain, Human 17-Beta-hydroxysteroid dehydrogenase type 1 mutant protein and Human Topoisomerase II alpha that are expressed more during Breast Cancer. The findings of this study imply that the test compound has potential for further study. [Display omitted] •2-Hydroxy benzaldehyde thiosemicarbazone and 4-Hydroxy benzaldehyde thiosemicarbazone were synthesized and characterized.•Cytotoxic activity of the ligand against MCF-7 human breast cancer cell line showed growth inhibition potential of the test compound.•Gene expression and protein expression study showed upregulation of tumor suppressor genes and downregulation of oncogenes.•Molecular docking result showed that both 2-HBTSc and 4-HBTSc have the potential to inhibit enzymes that are expressed more during Breast Cancer.•4-Hydroxy benzaldehyde thiosemicarbazone exhibited a better anticancer activity.