Activity of N-phenylbenzamide analogs against the neglected disease pathogen, Schistosoma mansoni

• Published in: Bioorganic & medicinal chemistry letters 2023-02, Vol.82, p.129164-129164, Article 129164
• Main Authors: Kanyanta, Masebe, Lengwe, Chilufya, Mambwe, Dickson, Francisco, Karol R., Liu, Lawrence J., Uli Sun, Yujie, Amarasinghe, Dilini K., Caffrey, Conor R., Mubanga Cheuka, Peter
• Format: Article
• Language: English
• Subjects: Animals; Antischistosomal agents; HEK293 Cells; Humans; N-phenylbenzamide analogs; Neglected Diseases; Schistosoma mansoni; Schistosomiasis mansoni - drug therapy; Schistosomicides - pharmacology; Schistosomicides - therapeutic use
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2023.129164

[Display omitted] 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 CC50 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 (EC50 = 80 nM), translating to a selectivity index of 123 over HEK 293 cells. The data encourage the further investigation of N-phenylbenzamides as antischistosomals.