Objective: Despite the optimal use of available anti-helminthetic drugs (AHDs), many patients with worm infections fail to experience worm control and others do so only at the expense of significant toxic side effects. The limitations with the conventional AHDs highlighted the need for developing newer agents to treat worm infestations. Method: A series of 3-(2-substituted) benzyl) thiazolidine-2, 4-diones (TND 1-9) were obtained by the condensation of thiazolidine-2, 4-diones with substituted aldehydes in presence of toluene and piperidine. The synthesized compounds were characterized by chromatographic, spectrometric methods, and elemental analysis. All the synthesized compounds, (TND 1-9) were screened for anthelmintic activity at two concentrations (20 and 40mg/ml), using adult earth worm Pheretima posthuma. The test compounds were found to possess significant anthelmintic activity. Result: Among the test compounds, compound 3-(4-(dimethylamino) cinnamoyl-ylidene) thiazolidine-2, 4-dione (TND 2) was found to exhibit potent anthelmintic activity with significantly shorter paralyzing time and the death of worms when compared to the reference standard piperazine.  The compound 3-(2-hydroxyphenyl) ethyl) thiazolidine-2,4-dione (TND 4) showed equipotent activity to that of the standard drug. Conclusion: Since, the compound 3-(4-(dimethylamino) cinnamoyl-ylidene) thiazolidine-2, 4-dione exhibited moderately more potent activity than the reference standard piperazine, it can be selected as a lead molecule for further worm exploitation.

KEY WORDS: anthelmintic, worm infections, new drugs, thiazolidine 2,4-dione, piperazine, 3-(2-substituted) benzyl) thiazolidine-2, 4-diones.