Design, one-pot synthesis and biological evaluation of imidazo[2,1-b] [1,3,4] thiadiazole derivatives for their anti- tubercular and anti-fungal activity

Abstract

In the present designed work, we have synthesized imidazo[2,1-b][1,3,4]thiadiazole derivatives (6a1-a6 to 6d1-d6) by reaction of compound 3 with appropriate α-haloaryl ketones produce substituted imidazo thiadiazole derivatives (4a-d). In the next step, these compounds (4a-d) undergoes the Vilsmeier reaction to introduce formyl group on the substituted arylimidazo[2,1-b][1,3,4]thiadiazole derivatives to form carbaldehyde derivatives (5a-d) and finally in the last step of the reaction for the synthesis of designed molecules, a one-pot synthetic procedure was used. For this, the one-pot reaction of 5a-d, thiosemicarbazide and substituted α-haloaryl ketones were reacted together in different reaction condition in ethanol solvent at an optimum temperature around 80°C produces a corresponding derivatives (6a1-a6 to 6d1-d6) with a better yield. The IR, 1H-NMR, and mass spectroscopy techniques were used to confirm the structure of final products and all synthesized molecules were tested for anti-TB and anti-fungal activity. The compounds 6a1, 6a2, 6a3, 6c1, 6c6 and 6d1 with MIC 1.6-6.25 μgm/ml displayed very good antitubercular and 6a1, 6a4, 6a5, and 6d1 displayed very good antifungal activity with MIC 5 μgm/ml due to electron withdrawing groups at 4th position to both phenyl rings which are attached to the thiazole of the imidazo thiadiazole and imidazo thiadiazole ring.