Influence of Indole-<i>N</i> Substitution of Thiosemicarbazones in Cationic Ru(II)(η<sup>6</sup>-Benzene) Complexes on Their Anticancer Activity
Nithya Balakrishnan, Jebiti Haribabu, Mahendiran Dharmasivam, Jayachandra Prakasan Jayadharini, Anantha Krishnan Dhanabalan, Srividya Swaminathan, Nattamai Bhuvanesh, César Echeverría, Ramasamy Karvembu
Abstract
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 Ru II -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.