Abstract：
Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 μM and ≤ 41 μM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 μM), 1e (IC50 4.8 μM), and 1i (IC50 5.2 μM) exhibited potencies equivalent to MTZ (IC50 4.9 μM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 μM) and 48 h (IC50 2.1 μM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 μM) or low cytotoxicity (CC50 between 69 and 100 μM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.
摘要：
滴虫病,由原生动物阴道毛滴虫引起的普遍性传播感染（STI），在全球范围内具有越来越重要的意义。近年来，由于其与感染和传播人类免疫缺陷病毒（HIV）和其他性传播感染的风险增加有关，其相关性有所增加。此外,许多出版物揭示了毛滴虫病和某些癌症之间的潜在联系。甲硝唑(MTZ),硝基咪唑化合物在50多年前发展起来，仍然是治疗的首选药物。然而,有关遗传毒性和副作用的报道强调了新化合物解决这一紧迫的全球健康问题的必要性.在这项研究中,我们合成了10个吡唑-硝基咪唑1（a-j）和4-硝基-1-（羟乙基）-1H-咪唑2，甲硝唑（MTZ）的类似物，并评估了它们的滴虫和细胞毒性作用。所有化合物1(a-j)和2的IC50值≤20μM和≤41μM,24小时和48小时后，分别。化合物1d(IC505.3μM),1e(IC504.8μM),和1i(IC505.2μM)表现出相当于MTZ(IC504.9μM)的效力，参考药物，24小时后。值得注意的是，化合物1i在24小时（IC505.2μM）和48小时（IC502.1μM）后显示出高抗滴虫活性。此外,所有化合物均显示对HeLa细胞无细胞毒性(CC50>100μM)或低细胞毒性(CC50在69和100μM之间)。这些发现表明，吡唑-硝基咪唑衍生物代表了一个有前途的杂环系统，作为进一步优化滴虫化疗的潜在线索。
