Trypanocidal and cytotoxic evaluation of synthesized thiosemicarbazones as potential drug leads against sleeping sickness

Abstract

Thiosemicarbazones have become one of the promising compounds as new clinical candidates due to their wide spectrum of pharmaceutical activities. The wide range of their biological activities depends generally on their related aldehyde or ketone groups. Here, we report the pharmacological activities of some thiosemicarbazones synthesized in this work. Benzophenone and derivatives were used with N(4)-phenyl-3-thiosemicarbazide to synthesize corresponding five thiosemicarbazones (1–5). Their structures were characterized by spectrometrical methods analysis IR, NMR 1H&13C and MS. The compounds were then screened in vitro for their antiparasitic activity and toxicity on Trypanosoma brucei brucei and Artemia salina Leach respectively. The selectivity index of each compound was also determined. Four thiosemicarbazones such as 4, 2, 3 and 1 reveal interesting trypanocidal activities with their half inhibitory concentration (IC50) equal to 2.76, 2.83, 3.86 and 8.48 lM respectively, while compound 5 (IC50 = 12.16 lM) showed a moderate anti-trypanosomal activity on parasite. In toxicity test, except compound 1, which showed a half lethal concentration LC50[281 lM, the others exerted toxic effect on larvae with LC50 of 5.56, 13.62, 14.55 and 42.50 lM respectively for thiosemicarbazones 4, 5, 3 and 2. In agreement to their selectivity index, which is greater than 1 (SI [1), these compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. The thiosemicarbazones 2–5 that displayed significant anti-trypanosomal and cytoxicity activities are suggested to have anti-neoplastic and anti-cancer activities.