Exploring the interaction between calf thymus DNA and 11H-Indeno[1,2-b]quinoxalin-11-one Thiosemicarbazones: Spectroscopies and in vitro antitumor activity.

Understanding the interactions between small molecules and calf thymus deoxyribonucleic acid (ctDNA) is critical for certain aspects of drug discovery. In this study, three 11H-indeno[1,2-b]quinoxalin-11-one thiosemicarbazones were synthesized and their interaction with ctDNA was examined through various spectroscopic techniques, including ultraviolet (UV) spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectrum, and through physicochemical methods, including viscosity measurements. In addition, the effects of these thiosemicarbazone compounds 4a, 4b and 4c on several cancer cell lines were explored. The results of UV absorption, fluorescence quenching and CD experiments indicated that compounds 4a, 4b and 4c primarily bound to ctDNA by an intercalation. This mode of interaction was further corroborated by viscosity measurements. Docked poses of compound 4a revealed that it formed a crucial N position hydrogen bond with the DNA receptor. The chemical structure of compound 4a was further confirmed by X-ray crystallographic analysis. Through biological evaluation, it was found that the in vitro cytotoxicity of three compounds agreed with the order of their binding strength to ctDNA, indicating that the antitumor activity of these compounds correlated with their binding affinity to ctDNA.