Design, synthesis, and anti-tumor activities of novel triphenylethylene–coumarin hybrids, and their interactions with Ct-DNA

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 17; pp. 4785 - 4789
• Main Authors: Chen, Hua, Li, Shuai, Yao, Yuchao, Zhou, Likai, Zhao, Jianpeng, Gu, Yunjing, Wang, Kerang, Li, Xiaoliu
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2013; Elsevier
• Subjects: Animals; Anti-tumor activities; anticarcinogenic activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cattle; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; chloroplast DNA; Coumarin; Coumarins - chemistry; Coumarins - pharmacology; cytotoxicity; denaturation; DNA - metabolism; DNA binding property; Drug Design; Drug Screening Assays, Antitumor; fluorescence; Humans; Intercalating Agents - chemistry; Intercalating Agents - pharmacology; Life Sciences & Biomedicine; microwave radiation; Neoplasms - drug therapy; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Stilbenes - chemistry; Stilbenes - pharmacology; structure-activity relationships; Triphenylethylene; Anti-tumor activities; Coumarin; DNA binding property; Triphenylethylene; DOCKING; INHIBITORS; BINDING; DERIVATIVES
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.07.009

Novel triphenylethylene–coumarin hybrid derivatives containing different amounts of amino side chains were designed and synthesized in good yields under microwave radiation. The derivatives 5b–d which possessed two amino side chains (except morpholinyl) showed a broad-spectrum and good anti-proliferative activity against five tumor cells and low cytotoxicity in osteoblast. UV–vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation exhibited that compounds 10c, 5c, and 13c bearing amino side chain (except morpholinyl) on 4-phenyl had significant interactions with Ct-DNA by the intercalative mode of binding. Structure–activity relationships (SARs) analysis suggested that the amino alkyl chain would play an important role both in the compounds against tumor cells proliferation and their interactions with DNA.