Effect of 6,6-Substitution on 2,2'-Bipyridine and Probing Biomolecular Interaction Through Experimental and Computational Studies Towards Anticancer Potency.

The current study focuses on the cytotoxicity assessment of 6,6'-substituted 2,2'-bipyridine derivatives containing functional groups, namely methyl (-CH3, L1), acid (-COOH, L2), ester (-COOCH3, L3), semicarbozone (-CONHNH2, L4). The ligands exhibited high solubility in dimethyl sulfoxide (DMSO) and moderately soluble in dimethyl formamide (DMF), acetonitrile (ACN) and low solubility in water. The ligands display a significant π→π* transition in the region of 270 nm to 305 nm. The emission spectra of the ligands reveal a prominent band in the 300 nm to 450 nm range, with a Stokes shift of 120 cm- 1. UV-VIS spectra analysis, the ligands (L1-L4, 1mM) demonstrated stability in various environmental like water, glutathione (GSH, 1mM), and MTT condition (10% DMSO). The interaction of ligands with DNA was assessed through calf thymus deoxyribonucleic acid (ctDNA) binding assay, viscosity studies, and ethidium bromide (EtBr) displacement assay, with L1 and L4 exhibiting the highest interaction. The MTT assay was conducted for 24 h and 48 h using ligands (L1-L4) and doxorubicin in MCF-7, HeLa, and L929 cell lines. Ligand L4 showed high potency IC50 values after 48 h in MCF-7 (1.28 µM) and HeLa (1.81 µM), but its potency is lower than doxorubicin. Overall, for the first time these results suggest that L4 has high anticancer activity at lower concentrations against breast and cervical cancers.