Pharmacology

Biography

Biography: Alex Joseph

Abstract

Thiazolidin-4-ones and coumarins are important pharmacodynamic heterocyclic scaffolds which have been reported to possess potent anti-inflammatory and anticancer properties. The combination of two pharmacophores on the same molecule is a well-established approach for the designing of potent molecules and further substitution on these scaffolds may further enhance their activity. Therefore a series of coumarin substituted thiazolidin-4-ones were synthesized and evaluated for their anticancer activity. Initially 3-acetylamiocoumarin was synthesized by cyclocondensation of salicyladehyde with N-acetylglycine. Acid hydrolysis of 3-acetylaminocoumarin afforded 3-aminocoumarin. Finally one pot reaction of 3-aminocoumarin and thioglycolic acid with different aldehydes in dry toluene yielded the corresponding coumarin substituted thiazolidin-4-ones. Structures of final compounds were confirmed by IR, NMR and Mass techniques. Among the fifteen coumarin substituted thiazolidin-4-ones screened for their in vitro cytotoxic effect on T47D and HeLa human cancer cell lines, compounds, 2-(3-fluorophenyl)-3-(2-oxo-2H-chromen-3-yl)thiazolidin-4-one (NKT-7), 2-(2-fluorophenyl)-3-(2-oxo-2H-chromen-3-yl)thiazolidin-4-one (NKT-8) and 2-(5-methylthiophen-2-yl)-3-(2-oxo-2H-chromen-3-yl) thiazolidin-4-one (NKT-14) exhibited maximum cytotoxicity with IC50 values below 2.5 µg/ml. Other moderately active compounds were NKT-4, NKT-5, NKT-6, NKT-7, NKT-13 and NKT-15 showing IC50 value between 3.45-14.67 µg/ml. The most active compounds NKT-7, NKT-8 and NKT-14 exhibited apoptosis mediated cell death as confirmed by Hoechst staining studies. Thiophen substituted thiazolidin-4-ones and fluoro/bromo/nitro phenyl substituted thiazolidin-4-ones were found to more cytotoxic than other thiazolidinones. These novel leads molecules can be further modified and screened to improve their anticancer activity.