5-(4-(1H-菲咯并[9,10-d]咪唑-2-基)亚苄基)噻唑烷-2,4-二酮的合成作为有前途的 DNA 和血清白蛋白结合剂，并评价其抗肿瘤活性。

Synthesis of 5-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)benzylidene)thiazolidine-2,4-dione as promising DNA and serum albumin-binding agents and evaluation of antitumor activity.

机构信息

School of Chemistry and Biochemistry, Thapar Institute of Engineering & Technology, Patiala 147 001, India.

出版信息

Eur J Med Chem. 2019 Mar 15;166:267-280. doi: 10.1016/j.ejmech.2019.01.053. Epub 2019 Jan 26.

DOI:10.1016/j.ejmech.2019.01.053

Abstract

A series of phenanthro[9,10-d]imidazole/oxazole and acenaphtho[1,2-d]imidazole with different aryl groups at C2-position has been synthesized. These compounds were in vitro evaluated for antitumor activity against a panel of 60 human cancer cell lines. Compound 8 exhibits higher cytotoxicity towards leukemia, colon, melanoma, renal, and breast cancer cell lines than the other evaluated cell panels and low toxicity against normal cell line Hek293. The binding properties of compound 8 with DNA have been investigated with absorption, emission and circular dichroism as well as thermal denaturation experiments which indicate intercalation with base pairs of human and calf thymus DNA. The molecular docking and site-selective binding studies also reveal the predominant intercalation of compound 8 in base pairs of DNA. The interaction between thiazolidine based phenanthrene 8 and serum albumins (HSA and BSA), transport proteins, has also been explored which shows quenching of fluorescence through static mechanism. The thermodynamic parameters, obtained from van't Hoff relationship indicate the prevalence of hydrogen-bonding/hydrophobic interactions for the binding phenomenon.

摘要

已经合成了一系列在 C2 位具有不同芳基的菲并[9,10-d]咪唑/恶唑和吖萘并[1,2-d]咪唑。这些化合物在体外针对 60 个人类癌细胞系进行了抗肿瘤活性评估。化合物 8 对白血病、结肠、黑色素瘤、肾和乳腺癌细胞系的细胞毒性高于其他评估的细胞系，对正常细胞系 Hek293 的毒性较低。通过吸收、发射和圆二色性以及热变性实验研究了化合物 8 与 DNA 的结合特性，表明与人和小牛胸腺 DNA 的碱基对进行插入。分子对接和选择性结合研究也表明，化合物 8 主要在 DNA 的碱基对中进行插入。还探索了基于噻唑烷的菲 8 与运输蛋白（HSA 和 BSA）血清白蛋白之间的相互作用，表明通过静态机制猝灭荧光。从范特霍夫关系获得的热力学参数表明，结合现象主要是氢键/疏水相互作用。