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

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology Pub Date : 2024-02-12 DOI:10.1016/j.exppara.2024.108711

Anna Seetsi , David D. N'Da , Nthatisi Nyembe , Keisuke Suganuma , Tsepo Ramatla , Oriel Thekisoe

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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 trypanosomes and evaluated their cytotoxicity using Madin–Darby bovine kidney cells. The n-alkyl sub-series hybrids, 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 submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.

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合成的硝基呋喃妥因-三唑混合物对引起动物非洲锥虫病的锥虫的体外抗锥虫活性。

非洲动物锥虫病（AAT）是一种由布鲁西锥虫、维瓦克斯锥虫、伊万西锥虫和刚果锥虫引起的疾病，主要由采采蝇（这里可能是采采蝇的科/属学名？）人工合成的杀锥虫药物被用来控制非洲锥虫病，但由于出现了抗药性锥虫，药效有所下降。因此，有必要继续开发安全有效的新药。本研究的目的是评估新型硝基呋喃妥因化合物体外抗锥虫活性，以对抗引起 AAT 的锥虫（布鲁西锥虫、埃文西锥虫和刚果锥虫）。本研究评估了之前合成的十九种硝基呋喃妥因-三唑（NFT-TZ）杂交化合物对动物锥虫的作用，并使用马丁-达比牛肾细胞评估了它们的细胞毒性。正烷基亚系列杂交种 8（IC50 0.09 ± 0.02 μM；SI 686.45）和 9（IC50 0.07 ± 0.04 μM；SI 849.31）对布氏锥虫具有最高的抗锥虫活性。相反，壬基杂交种 6（IC50 0.12 ± 0.06 μM；SI 504.57）和硝基苄基杂交种 18（IC50 0.11 ± 0.03 μM；SI 211.07）对 T. evansi 的杀锥虫活性最高。壬基杂交种 6（IC50 0.02 ± 0.01 μM；SI 6328.76）与十一烷基杂交种 8（IC50 0.02 ± 0.01 μM；SI 3454.36）和 3-溴苄基杂交种 19（IC50 0.02 ± 0.01 μM；SI 2360.41）一样，也被检测出对刚果痢疾杆菌具有最强的杀胰活性。这些混合物对哺乳动物细胞的毒性作用较弱，而对锥虫的亚摩尔级抗寄生虫作用具有高度选择性，因此可将它们视为潜在的杀锥虫线索，供进一步的体内研究。

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来源期刊

Experimental parasitology 医学-寄生虫学

CiteScore

3.10

自引率

4.80%

发文量

160

审稿时长

3 months

期刊介绍： Experimental Parasitology emphasizes modern approaches to parasitology, including molecular biology and immunology. The journal features original research papers on the physiological, metabolic, immunologic, biochemical, nutritional, and chemotherapeutic aspects of parasites and host-parasite relationships.