Department of Chemistry, School of Natural Sciences, University of Zambia, P.O Box 32379, Lusaka, Zambia.
School of Medicine and Health Sciences, University of Lusaka, P.O Box 36711, Lusaka, Zambia.
Bioorg Med Chem Lett. 2023 Feb 15;82:129164. doi: 10.1016/j.bmcl.2023.129164. Epub 2023 Jan 31.
For the Schistosoma mansoni flatworm pathogen, we report a structure-activity relationship of 25 derivatives of the N-phenylbenzamide compound, 1 (MMV687807), a Medicines for Malaria Venture compound for which bioactivity was originally identified in 2018. Synthesized compounds were cross-screened against the HEK 293 mammalian cells. Compounds 9 and 11 were identified as fast-acting schistosomicidal compounds whereby adult worm integrity was severely compromised within 1 h. Against HEK 293 mammalian cells, both compounds exhibited high CC values (9.8 ± 1.6 and 11.1 ± 0.2 µM respectively) which could translate to comfortable selectivity. When evaluated in a concentration-response format, compound 9 was active in the nanomolar range (EC = 80 nM), translating to a selectivity index of 123 over HEK 293 cells. The data encourage the further investigation of N-phenylbenzamides as antischistosomals.
对于曼氏血吸虫扁虫病原体，我们报告了 N- 苯基苯甲酰胺化合物 1（MMV687807）的 25 种衍生物的结构-活性关系，该化合物最初是 2018 年由疟疾药物倡议组织鉴定出具有生物活性的药物。合成的化合物在 HEK 293 哺乳动物细胞中进行了交叉筛选。化合物 9 和 11 被鉴定为快速杀血吸虫化合物，在 1 小时内严重破坏成虫的完整性。对 HEK 293 哺乳动物细胞，这两种化合物均表现出较高的 CC 值（分别为 9.8±1.6 和 11.1±0.2 μM），这可能意味着具有较高的选择性。当以浓度反应的形式进行评估时，化合物 9 在纳摩尔范围内具有活性（EC=80 nM），对 HEK 293 细胞的选择性指数为 123。这些数据鼓励进一步研究 N- 苯基苯甲酰胺作为抗血吸虫药物。
