Identification of potent and orally efficacious phosphodiesterase inhibitors in Cryptosporidium parvum-infected immunocompromised male mice.

ABSTRACT: Cryptosporidium parvum and C. hominis are parasites that cause life-threatening diarrhea in children and immunocompromised people. There is only one approved treatment that is modestly effective for children and ineffective for AIDS patients. Here, screening 278 compounds from the Merck KGaA, Darmstadt, Germany collection and accelerated follow-up enabled by prior investigation of the compounds identifies a series of pyrazolopyrimidine human phosphodiesterase (PDE)-V (hPDE-V) inhibitors with potent anticryptosporidial activity and efficacy following oral administration in C. parvum-infected male mice. The lead compounds affect parasite host cell egress, inhibit both C. parvum and C. hominis, work rapidly, and have minimal off-target effects in a safety screening panel. Interestingly, the h

SUBMITTER: Ajiboye J 

PROVIDER: S-EPMC11436873 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature