2-(Nitroaryl)-5-Substituted-1,3,4-Thiadiazole Derivatives with Antiprotozoal Activities: In Vitro and In Vivo Study.

Nitro-containing compounds are a well-known class of anti-infective agents, especially in the field of anti-parasitic drug discovery. HAT or sleeping sickness is a neglected tropical disease caused by a protozoan parasite, . Following the approval of fexinidazole as the first oral treatment for both stages of HAT, there is an increased interest in developing new nitro-containing compounds against parasitic diseases. In our previous projects, we synthesized several megazole derivatives that presented high activity against promastigotes. Here, we screened and evaluated their trypanocidal activity. Most of the compounds showed submicromolar IC against the BSF form of (STIB 900). To the best of our knowledge, compound is one of the most potent nitro-containing agents reported against HAT in vitro. Compound revealed an acceptable cure rate in the acute mouse model of HAT, accompanied with noteworthy in vitro activity against , , and . Taken together, these results suggest that these compounds are promising candidates to evaluate their pharmacokinetic and biological profiles in the future.