科研之友
微信
新浪微博
Facebook
分享链接
摘要
<jats:title>Abstract</jats:title><jats:p>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 (<jats:bold>4 a‐q</jats:bold>) and evaluated their antioxidant, anticancer and DNA binding properties. Among all the analogs, compounds with <jats:italic>o</jats:italic>‐chloro (<jats:bold>4b</jats:bold>), <jats:italic>o</jats:italic>‐fluoro (<jats:bold>4h</jats:bold>) and <jats:italic>p</jats:italic>‐fluoro (<jats:bold>4j</jats:bold>) substitution exhibited potent antioxidant activity and the potency of <jats:bold>4 b</jats:bold> was comparable to the standard ascorbic acid. In a cell based screen, compound <jats:bold>4 b</jats:bold> inhibited the growth of human cervical cancer (SiHa) and colorectal epithelial carcinoma (SW620) cancer cell lines with an IC<jats:sub>50</jats:sub> values of 67.99 and 48.96 μg mL<jats:sup>−1</jats:sup>, 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 <jats:bold>4 b</jats:bold>, <jats:bold>4 h</jats:bold> and <jats:bold>4 j</jats:bold> 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 <jats:bold>4 b</jats:bold> makes it a suitable candidate for further optimization and pharmacological studies.</jats:p>
- 出版日期2018-3-7
