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Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis.
- Source :
-
Nature communications [Nat Commun] 2019 Jun 27; Vol. 10 (1), pp. 2816. Date of Electronic Publication: 2019 Jun 27. - Publication Year :
- 2019
-
Abstract
- Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.
- Subjects :
- Amides adverse effects
Amides chemistry
Animals
Antiprotozoal Agents adverse effects
Antiprotozoal Agents chemistry
Boron Compounds adverse effects
Boron Compounds chemistry
Cryptosporidiosis parasitology
Cryptosporidium drug effects
Cryptosporidium growth & development
Drug Evaluation, Preclinical
Female
Humans
Isoxazoles adverse effects
Isoxazoles chemistry
Male
Mice
Rats
Amides administration & dosage
Antiprotozoal Agents administration & dosage
Boron Compounds administration & dosage
Cryptosporidiosis drug therapy
Isoxazoles administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31249291
- Full Text :
- https://doi.org/10.1038/s41467-019-10687-y