Design, synthesis, and in vitro evaluation of thiosemicarbazone derivatives as anti-filarial agents.

Effective macrofilaricidal drugs are not commercially available, and in an endeavour to find out new macrofilaricidal agents, in this research work, thiosemicarbazone derivatives have been prepared and tested against adult Setaria digitata, a cattle filarial parasite, as a model nematode for the filarial parasite, Wuchereria bancrofti. Lipinski and Veber rules have been used to design these molecules and found out that all the designed molecules show drug-like molecular properties. The in vitro anti-filarial potential of thiosemicarbazones against S. digitata was carried out using worm motility and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction colorimetric assays at 100 μg/ml concentration for the incubation period of 24 h. The standard drugs used at present for filaria, Albendazole, Ivermectin and Diethylcarbamazine were not able to kill the adult filarial worms effectively. In contrast, phenyl thiosemicarbazones with trifluoromethyl substitution at 3rd and 4th positions, 2-pyrrolyl, and isatinyl made the adult worms immotile and also showed 69%–83% inhibition in formazan formation an indicator of non viability. [Display omitted] • At present, no macrofilaricidal drugs are available in the market. • Adult Setaria digitata , a cattle filarial parasite was used as a model for Wuchereria bancrofti. • In vitro MTT reduction colorimetric assay at 100 μg/ml concentration used. • Albendazole, Ivermectin and Diethylcarbamazine showed 17.5%, 35.1% and 23.2% inhibition in formazan formation respectively. • Phenyl thiosemicarbazones with trifluoromethyl, 2-pyrrolyl, and isatinyl showed better macrofilaricidal activity with 69%–83% inhibition. [ABSTRACT FROM AUTHOR]