N-Substituted 1,2,3-Triazolyl-Appended Indole-Chalcone Hybrids as Potential DNA Intercalators Endowed with Antioxidant and Anticancer Properties

Despite the fact that many small molecule inhibitors have been approved for cancer therapy, we still have a mighty long road to traverse in the field of targeted therapy against cancer. In order to overcome the challenges of chemo resistance and selectivity, we designed and synthesized 1,2,3-triazole appended indole-chalcone derivatives (4a-q) and evaluated their antioxidant, anticancer and DNA binding properties. Among all the analogs, compounds with o-chloro (4b), o-fluoro (4h) and p-fluoro (4j) substitution exhibited potent antioxidant activity and the potency of 4b was comparable to the standard ascorbic acid. In a cell based screen, compound 4b inhibited the growth of human cervical cancer (SiHa) and colorectal epithelial carcinoma (SW620) cancer cell lines with an IC50 values of 67.99 and 48.96 g mL(-1), respectively without showing any significant cytotoxicity in human embryonic kidney cells (HEK293) at the similar concentration. To gain insight into the DNA-binding ability, various spectroscopic techniques such as UV-visible, fluorescence, circular dichroism, viscosity and cyclic voltametric studies were performed. These studies exposed that compounds 4b, 4h and 4j act via non-covalent intercalative mode of binding to DNA causing their antiproliferative activity, supported by molecular docking studies. Our study revealed the non-toxic nature and potent activity of compound 4b makes it a suitable candidate for further optimization and pharmacological studies.