title: Combretastatin A-4 derivatives: synthesis and evaluation of 2,4,5-triaryl-1H-imidazoles as potential agents against H1299 (non-small cell lung cancer cell).
abstract: A number of 2,4,5-triaryl-1H-imidazole derivatives were synthesized and evaluated for their antiproliferative activities against the growth of five cell lines including three non-small cell lung cancers (H460, H1299, and A549), one breast cancer (MCF-7), and one normal diploid embryonic lung cell line (MRC-5). Preliminary results indicated that both 2-(5-bromofuran-2-yl)-4,5-bis{4-[3-(dimethylamino) propoxy] phenyl}-1H-imidazole (10f) and 4,5-bis{4-[3-(dimethylamino)propoxy]phenyl}-2-(5-nitrofuran-2-yl)-1H -imidazole (10g) were selectively active against the growth of H1229 with an IC(50) of less than 0.1 μM, thus were more active than topotecan (IC(50) > 10.0 μ M). However, both 10f and 10g exhibited only marginal cytotoxicity against H460, A549, MCF-7, and MRC-5 requiring an IC (50) of at least 4.16 μM. Our results also indicated that 10f induced H1299 cell cycle arrest at G0/G1 through the inactivation of p38 MAPK, JNK, ERK, as well as the expression of SIRT1 and survivin. These results suggested that 10f might have therapeutic potential against H1299 (non-small cell lung cancer cell).
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.forename: Chi-Yi
authors.initials: CY
authors.lastname: Li
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chiu
authors.forename: Huei-Ting
authors.initials: HT
authors.lastname: Hu
authors.forename: Chein-Hwa
authors.initials: CH
authors.lastname: Han
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Cherng-Chyi
authors.initials: CC
authors.lastname: Tzeng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D015151:Immunoblotting; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D044366:Transition Temperature
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D013267:Stilbenes; C058728:fosbretabulin