title: Synthesis and evaluation of bis-thiazole derivatives as new anticancer agents.
abstract: New bis-thiazole derivatives (1-10) were synthesized via the ring closure of 1,1'-(3,3'-dimethoxybiphenyl-4,4'-diyl)bis(thiourea) with phenacyl bromides and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma, 5RP7 H-ras oncogene transformed rat embryonic fibroblast and NIH/3T3 mouse embryonic fibroblast cell lines using MTT assay. DNA synthesis inhibitory effects of these compounds were investigated. Each derivative was also evaluated for its ability to inhibit AChE and BuChE using a modification of Ellman's spectrophotometric method. Among these compounds, 3,3'-dimethoxy-N(4),N(4)'-bis(4-(4-bromophenyl)thiazol-2-yl)-[1,1'-biphenyl]-4,4'-diamine (5) can be identified as the most promising anticancer agent due to its notable inhibitory effects on A549 and C6 cell lines and low toxicity to NIH/3T3 cell lines. Compound 5 exhibited anticancer activity against A549 and C6 cell lines with IC50 values of 37.3 ± 6.8 μg/mL and 11.3 ± 1.2 μg/mL, whereas mitoxantrone showed anticancer activity against A549 and C6 cell lines with IC50 values of 15.7 ± 4.0 μg/mL and 11.0 ± 1.7 μg/mL, respectively. Furthermore, compound 5 showed DNA synthesis inhibitory activity against A549 cell line.
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Gülhan
authors.initials: G
authors.lastname: Turan-Zitouni
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey. Electronic address: mdaltintop@anadolu.edu.tr.
authors.forename: Mehlika Dilek
authors.initials: MD
authors.lastname: Altıntop
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Özdemir
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Zafer Asım
authors.initials: ZA
authors.lastname: Kaplancıklı
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Biochemistry, 26470 Eskişehir, Turkey.
authors.forename: Gülşen Akalın
authors.initials: GA
authors.lastname: Çiftçi
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Biochemistry, 26470 Eskişehir, Turkey.
authors.forename: Halide Edip
authors.initials: HE
authors.lastname: Temel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D041681:NIH 3T3 Cells / Q000187:drug effects; D051381:Rats; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D013844:Thiazoles; D004247:DNA; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Anticancer activity; Bis-thiazole; Butyrylcholinesterase; DNA synthesis inhibitory activity