Synthesis and biological activity of isatines bearing thiazolidinone and pyrazoline moieties

Abstract

The synthesis and antitumor activity screening of isatin-pyrazoline hybrids and isatin based conjugates with thiazolidine moiety were performed. Reaction of 2-chloro-N-arylacetamides or 2-chloro1-(3-naphtalene-2-yl-5-aryl-4,5- dihydropyrazol-1-yl)-ethanones and isatines yielded corresponding N-substituted isatines (1a-1c and 2a-2d). The compounds 1a-1c have been used in Knoevenagel condensation with 4-thiazolidinones for obtaining a series of 5-ylidenederivatives 3a-3e, 4a-4b. Eight the synthesized compounds were tested for their anticancer activity in NCI60 cell lines. Among the tested istin-pyrazoline conjugates 5-bromo-1-{2-[5-(4-methoxyphenyl)-3-naphthalen-2-yl- 4,5-dihydropyrazol-1-yl]-2-oxoethyl}-1H-indole-2,3-dione (2c) was found to be the most active candidate with selective influence on leukemia subpanel tumor cell lines with pGI50 values range of 5.49-5.75. The chemical modification of N-substituted isatines (1a-1c) allowed us to identify 2-[3-(2-amino-4-oxo-4H- thiazol-5-ylidene)-2-oxo-2,3-dihydroindol1-yl]-N-(2-trifluoromethylphenyl) -acetamide (2c), which showed inhibition activity with average pGI50/pTGI values 5.03 / 4.43 and the highest influence on SR leukemia cell line (pGI50 = 6.23). (Chemical Equation Presented).