In vitro antitrypanosomal activity of synthesized nitrofurantoin-triazole hybrids against Trypanosoma species causing animal African trypanosomosis

Abstract

Animal African trypanosomosis (AAT) is a disease caused by Trypanosoma brucei brucei, T. vivax, T. evansi and T. congolense which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the in vitro anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal try- panosomes and evaluated their cytotoxicity using Madin-Darby bovine kidney cells. The n-alkyl sub-series hy-brids, 8 (IC50 0.09 ± 0.02 μM; SI 686.45) and 9 (IC50 0.07 ± 0.04 μM; SI 849.31) had the highest anti-trypanosomal activity against T. b. brucei. On the contrary, the nonyl 6 (IC50 0.12 ± 0.06 μM; SI 504.57) and nitrobenzyl 18 (IC50 0.11 ± 0.03 μM; SI 211.07) displayed the highest trypanocidal activity against T. evansi. The nonyl hybrid 6 (IC50 0.02 ± 0.01 μM; SI 6328.76) was also detected alongside the undecyl 8 (IC50 0.02 ± 0.01 μM; SI 3454.36) and 3-bromobenzyl 19 (IC50 0.02 ± 0.01 μM; SI 2360.41) as the most potent hybrids against T. congolense. These hybrids had weak toxicity effects on the mammalian cells and highly selective sub- micromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.