Indole thiosemicarbazones (TSCs)
and their complexes are known
to possess various biological activities. The variation in anticancer
activity with different indole-N substituents of
TSCs in the RuII-benzene complexes (C1–C7) was studied. The complexes were adequately characterized
using analytical and spectroscopic techniques. The single crystal
X-ray diffraction (XRD) technique confirmed the piano-stool structure
of the complexes (C4 and C7). The theoretical
findings on the structure of complexes supported the experimental
results. The complexes (C1–C7) exhibited
good biomolecular interactions with DNA/protein and significant anticancer
potential against MB-MDA-231 and MCF-7 cancer cells. Also, the complexes
were least toxic to normal human cells, suggesting the selectivity
of the complexes. The benzyl substituent at indole-N of the TSC ligands seemed to improve the cytotoxic profile of their
complexes compared to the allyl one. Among the benzyl scaffolds, the para-substituted [methyl (C5) and chloro (C6)] ones elevated the anticancer activity compared to the meta-substituted compounds (C4 and C7). Hoechst and AO–EB staining assisted the visualization of
the apoptotic changes induced by active complexes C2 and C6 in MB-MDA-231 cells. Further, flow cytometric analysis
authenticated the cell cycle arrest in the sub-G0/G1 phase. Western
blotting studies confirmed the apoptotic mode of cell death by quantifying
the proapoptotic and antiapoptotic proteins.