Cytotoxicity and DNA binding property of phenanthrene imidazole with polyglycol side chains

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 20; pp. 6347 - 6351
• Main Authors: Wang, Shuxiang, Li, Hongdong, Chen, Chao, Zhang, Jinchao, Li, Shenghui, Qin, Xinying, Li, Xiaoliu, Wang, Kerang
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.10.2012; Elsevier
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; binding capacity; Binding property; Biological and medical sciences; Cancer; Cell Line, Tumor; Chemistry; Chemistry, Medicinal; Chemistry, Organic; chloroplast DNA; Cisplatin; Cytotoxicity; denaturation; DNA; DNA - metabolism; double prime KB cells; Fluorescence; Glycols - chemistry; Glycols - pharmacology; Humans; imidazole; Imidazoles - chemistry; Imidazoles - pharmacology; Intercalating Agents - chemistry; Intercalating Agents - pharmacology; Intercalation; Life Sciences & Biomedicine; Medical sciences; N.M.R; Neoplasms - drug therapy; nuclear magnetic resonance spectroscopy; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Phenanthrene; Phenanthrene imidazole derivatives; Phenanthrenes - chemistry; Phenanthrenes - pharmacology; Physical Sciences; polyglycol; Polyglycol side chain; Science & Technology; Spectroscopy; Thermal denaturation; Tumor cell lines; Cytotoxicity; Polyglycol side chain; Phenanthrene imidazole derivatives; Binding property; POTENT; CLEAVAGE; Imidazole derivatives; Phenanthrene derivatives; Biological fixation; Side chain; DNA; Imidazole
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.08.079

A series of phenanthrene imidazole with polyglycol side chain (2a–2c and 3a–3c) were synthesized and characterized by IR, NMR and MS. The cytotoxicity of 2a–2c and 3a–3c against cancer cell lines (HL-60, BGC-823, Bel-7402 and KB) in vitro were measured using MTT method. The DNA binding properties of 3a–3c were investigated by UV, fluorescence, CD spectroscopies and thermal denaturation. The results indicate that 2a exhibits higher cytotoxicity than cisplatin against BGC-823 and Bel-7402 cell lines, 3b and 3c exhibit higher cytotoxicity than 2b and 2c against BGC-823, Bel-7402 and KB cell lines. The cytotoxic effect of 2a–2c decrease with the increase of side chains length, the cytotoxic effect of 3a–3c increased with the increasing length of side chains against BGC-823, Bel-7402 and KB cell lines. Compounds 3a–3c intercalated DNA with a vertical orientation in the intercalation pocket. The binding constants of 3a–3c with Ct-DNA are 1.68×106, 1.51×106 and 0.709×106M−1, respectively. The binding affinity of 3a–3c with Ct-DNA trended to decrease with the increasing length of polyglycol side chains.