Unit for Environmental Sciences and Management, North-West University, Potchefstroom, 2531, South Africa.
Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom, 2521, South Africa.
Exp Parasitol. 2024 Apr;259:108711. doi: 10.1016/j.exppara.2024.108711. Epub 2024 Feb 12.
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 trypanosomes and evaluated their cytotoxicity using Madin-Darby bovine kidney cells. The n-alkyl sub-series hybrids, 8 (IC 0.09 ± 0.02 μM; SI 686.45) and 9 (IC 0.07 ± 0.04 μM; SI 849.31) had the highest anti-trypanosomal activity against T. b. brucei. On the contrary, the nonyl 6 (IC 0.12 ± 0.06 μM; SI 504.57) and nitrobenzyl 18 (IC 0.11 ± 0.03 μM; SI 211.07) displayed the highest trypanocidal activity against T. evansi. The nonyl hybrid 6 (IC 0.02 ± 0.01 μM; SI 6328.76) was also detected alongside the undecyl 8 (IC 0.02 ± 0.01 μM; SI 3454.36) and 3-bromobenzyl 19 (IC 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 submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.
动物非洲锥虫病（AAT）是由布氏锥虫、布氏锥虫、伊氏锥虫和刚果锥虫引起的疾病，主要通过采采蝇（也许这里是采采蝇科/属的学名？）传播。合成的杀锥虫药物用于控制 AAT，但由于出现耐药锥虫，疗效降低。因此，需要继续开发新的安全有效的药物。本研究旨在评估新型硝呋太尔化合物对引起 AAT 的锥虫（布氏锥虫、伊氏锥虫和刚果锥虫）的体外抗锥虫活性。本研究评估了之前合成的十九个硝呋太尔-三唑（NFT-TZ）杂化物对动物锥虫的作用，并使用马迪恩-达比牛肾细胞评估了它们的细胞毒性。正烷基亚系列杂化物 8（IC 0.09±0.02μM；SI 686.45）和 9（IC 0.07±0.04μM；SI 849.31）对布氏锥虫的抗锥虫活性最高。相反，壬基 6（IC 0.12±0.06μM；SI 504.57）和硝基苄基 18（IC 0.11±0.03μM；SI 211.07）对伊氏锥虫显示出最高的杀锥虫活性。还检测到壬基杂化物 6（IC 0.02±0.01μM；SI 6328.76）与十一基 8（IC 0.02±0.01μM；SI 3454.36）和 3-溴苄基 19（IC 0.02±0.01μM；SI 2360.41）一起作为针对 T. congolense 的最有效杂化物。这些杂化物对哺乳动物细胞的毒性作用较弱，对寄生虫具有高度选择性的亚微摩尔抗寄生虫作用，因此它们可以被视为进一步体内研究的潜在杀锥虫先导化合物。
