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Synthesis and Antitumor Evaluation of New Polysubstituted Thiazole and Derived Thiazolo[4, 5‐ d ]pyrimidine Systems
Author(s) -
Fahmy Hesham T. Y.,
Rostom Sherif A. F.,
Bekhit Adnan A.
Publication year - 2002
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(200205)335:5<213::aid-ardp213>3.0.co;2-h
Subject(s) - thiazole , pyrimidine , pyrazole , chemistry , stereochemistry , in vitro , cell culture , selectivity , biochemistry , biology , genetics , catalysis
The synthesis of three categories of compounds containing the 1 H ‐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‐1 H ‐pyrazole‐4‐methylidenehydrazinocarbonyl)thiazole‐2(3 H )‐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 μM, 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‐1 H ‐pyrazole‐4‐methylidenehydra‐zinocarbonyl) thiazole‐2(3 H )‐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 μM and TGI MG‐MID values of 55.5—95.5 μM.