title: Synthesis and antitumor evaluation of new polysubstituted thiazole and derived thiazolo[4, 5-d]pyrimidine systems.
abstract: The synthesis of three categories of compounds containing the 1H-pyrazole ring linked to some dihydrothiazoles, thiazolidinones, and thiazolo[4, 5-d]pyrimidines through different linkages is described. Nine of the newly synthesized target compounds were selected by the NCI for in-vitro antitumor screening. Four compounds, namely 4a, 4b, 13, and 14, exhibited a broad spectrum of antitumor activity against most of the tested tumor cell lines. Compound 4a, 3-phenyl-4-amino-5-(3, 5-dimethyl-1-phenyl-1H-pyrazole-4-methylidenehydrazinocarbonyl)thiazole-2(3H)-thione proved to be the most active antitumor agent in the present study with GI(50), TGI, and LC(50) MG-MID values of 3.93, 41.7, and 91.2 microM, respectively. The same compound also exhibited high selectivity towards CNS SNB-75 and Ovarian IGROV1 cancer cell lines at both the GI(50) and TGI levels. Compound 4b, 3-(4-chlorophenyl)-4-amino-5-(3, 5-dimethyl-1-phenyl-1H-pyrazole-4-methylidenehydra-zinocarbonyl) thiazole-2(3H)-thione showed nearly the same pattern of activity as 4a but to a lesser extent. Compounds 13 and 14 displayed moderate antitumor activity against most of the tested tumor cell lines with GI(50) MG-MID values range of 20.4-80.6 microM and TGI MG-MID values of 55.5-95.5 microM.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, AR Egypt.
authors.forename: Hesham T Y
authors.initials: HT
authors.lastname: Fahmy
authors.forename: Sherif A F
authors.initials: SA
authors.lastname: Rostom
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Bekhit
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles