Synthesis and in vitro anti-trypanosomal evaluation of quinolone hydrazide analogues

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African trypanosomiasis is a major health threat to humans and animals in 36 countries within sub-Saharan Africa. We previously identified quinolone hydrazides exhibiting sub-micromolar anti-trypanosomal activity. However, the most potent compounds had poor aqueous solubility of <5 µM, hindering advancement to efficacy studies in animals. Accordingly, we generated a series of nine quinolone hydrazide analogues and evaluated in vitro anti-trypanosomal activity, cell toxicity and selected physicochemical properties. Compounds 4 and 5 , exhibited potent anti-trypanosomal activity of 0.362 ± 0060 µM and 1.251 ± 0.295 µM, respectively and showed no toxicity (CC 50 > 20 µM) against HEK 293 cells. The two compounds showed slightly improved aqueous solubility of 5 µM when compared to the previously identified lead compounds and good LogD values (2–3).