Equipe Pharmaco-Chimie Radicalaire, CNRS, ICR UMR 7273, Faculté de Pharmacie, Aix Marseille University, 27 Boulevard Jean Moulin, CS30064, CEDEX 05, 13385 Marseille, France.
Assistance Publique-Hôpitaux de Marseille (APHM), Pharmacie Usage Intérieur, Hôpital Nord, Chemin-des-Bourrely, 13015 Marseille, France.
Molecules. 2022 Mar 27;27(7):2163. doi: 10.3390/molecules27072163.
Human American trypanosomiasis, called Chagas disease, caused by protozoan infection, represents a major public health problem, with about 7000 annual deaths in Latin America. As part of the search for new and safe anti- derivatives involving nitroheterocycles, we report herein the synthesis of ten 1-substituted 2-nitropyrrole compounds and their biological evaluation. After an optimization phase, a convergent synthesis methodology was used to obtain these new final compounds in two steps from the 2-nitropyrrole starting product. All the designed derivatives follow Lipinski's rule of five. The cytotoxicity evaluation on CHO cells showed no significant cytotoxicity, except for compound (CC = 24.3 µM). Compound appeared to show activity against intracellular amastigotes form (EC = 3.6 ± 1.8 µM) and good selectivity over the vero host cells. Unfortunately, this compound showed an insufficient maximum effect compared to the reference drug (nifurtimox). Whether longer duration treatments may eliminate all parasites remains to be explored.
人体美洲锥虫病，又称恰加斯病，由原生动物感染引起，是拉丁美洲一个主要的公共卫生问题，每年约有 7000 人死亡。作为寻找涉及硝基杂环的新型和安全抗衍生物的一部分，我们在此报告了十种 1-取代的 2-硝基吡咯化合物的合成及其生物学评价。经过优化阶段，使用收敛合成方法从 2-硝基吡咯起始产物两步合成得到这些新的最终化合物。所有设计的衍生物都遵循 Lipinski 的五规则。对 CHO 细胞的细胞毒性评价表明，除化合物 （CC = 24.3 µM）外，没有明显的细胞毒性。化合物 似乎对细胞内无鞭毛体形式（EC = 3.6 ± 1.8 µM）具有活性，并且对 vero 宿主细胞具有良好的选择性。不幸的是，与参考药物（硝呋替莫）相比，该化合物 显示出的最大效果不足。是否更长时间的治疗可能消除所有寄生虫仍有待探索。
