Synthesis and biological activity evaluation of new thiazolidinone-diclofenac hybrid molecules

Abstract

A novel series of [2-(2,6-dichlorophenylamino)-phenyl]-acetic acid N -3-(substituted)-4-thiazolidin-5- ylidenemethyl-hydrazide derivatives has been designed and synthesized. The structures of synthe- 1 13 sized compounds were confirmed by their HNMR, C NMR and LCMS spectroscopic data. Target compounds were screened for their in vitro anticancer activity according to US NCI protocols, in vitro trypanocidal activity toward Trypanosoma brucei brucei (Tbb) and evaluated for anti-inflam- matory activity on the carrageenan edema model in rats. Biological screening data led to identifi- cation of compounds 3.3 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N -(4-oxo-2-thioxo- thiazolidin-5-ylidenemethyl)-hydrazide) and 3.7 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N -(4-oxo-2-thioxo-3-(3-trifluoromethylphenyl)thiazolidin-5-ylidenemethyl)-hydrazide) which demon- strated moderate antitumor activity on the non-small-cell lung cancer NCI-H522 and colon cancer HCT-116 cell lines. Several hit compounds (3.2, 3.4) exhibited the promising and significant inhib- ition growth of the parasites at micromolar concentrations (IC50 values of 4.8 and 7.06 lM, respect- ively). The synthesized compounds also demonstrated considerable anti-inflammatory effect comparable to the reference non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac sodium or ketorolac tromethamine.