Carborane-Functionalized Thiocarbohydrazones: Synthesis, Computational, and Anticancer Evaluation

Two
carborane-functionalized thiocarbohydrazone derivatives, TCH-m-CB and TCH-p-CB, were
synthesized and well-characterized. The anticancer potential of these
compounds was evaluated in vitro against the MCF-7
human breast cancer cell line and NIH/3T3 mouse embryo fibroblast
cell line. The cytotoxicity study shows that the meta-carborane derivative, TCH-m-CB, shows higher cytotoxicity toward cancer cells with
an IC50 value of 36.96 μM. The caspase-3 activity
assays confirmed that both compounds induce cell death through apoptosis.
The computational DFT studies indicated a higher HOMO–LUMO
energy gap for TCH-m-CB (3.870 eV) compared to TCH-p-CB (2.811 eV), indicating a higher
stability of the meta-carborane derivative, TCH-m-CB, in the
ground state. The molecular docking study shows that the thiocarbohydrazone
derivatives of carboranes exhibit stronger binding affinities to key
cancer-related protein targets (Erα, Topo IIα, and PARP-1)
than the reference drug, doxorubicin. The in silico analysis of the ADMET properties of thiocarbohydrazone derivatives
of carboranes also exhibits highly promising drug-like properties
as compared to the reference drug doxorubicin. Overall, the results
indicate that the carborane-functionalized thiocarbohydrazone derivatives
have the potential to be effective anticancer agents.