Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety.
Antitumor screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. Reactions of (benzothiazole-2-yl)hydrazine with trithiocarbonyl diglycolic acid or 6-methyl-2-aminobenzothiazole with 2-carbethoxymethylthio-2-thiazoline-4-one have yielded starting 3- (1) or 2-substituted (11) 4-thiazolidinones which have been subsequently utilized in a Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 2-10, 12-16. Compound 11 has been obtained alternatively by a counter synthesis method based on the reaction of 2-chloro-N-(6-methylbenzothiazol-2-yl)-acetamide and ammonium thiocyanate. The structures of compounds have been determined by (1)H, (13)C NMR, IR and X-ray analysis. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute and two (6, 16) of them has revealed the anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancers cell lines. Among tested compounds, 2-{2-[3-(benzothiazol-2-ylamino)-4-oxo-2-thioxothiazolidin-5-ylidenemethyl]-4-chlorophenoxy}-N-(4-methoxyphenyl)-acetamide (6) was found to be the most active candidate with average logGI(50) and logTGI values -5.38 and -4.45 respectively.
Havrylyuk
Dmytro
D
Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv 79010, Ukraine.
Mosula
Ludmyla
L
Zimenkovsky
Borys
B
Vasylenko
Olexandr
O
Gzella
Andrzej
A
Lesyk
Roman
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D013844:Thiazoles