Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum

Corey R Johnson; Suresh Kumar Gorla; Mandapati Kavitha; Minjia Zhang; Xiaoping Liu; Boris Striepen; Jan R Mead; Gregory D Cuny; Lizbeth Hedstrom

doi:10.1016/j.bmcl.2012.12.037

Back

Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum

Journal article

Open access

Peer reviewed

Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum

Corey R Johnson, Suresh Kumar Gorla, Mandapati Kavitha, Minjia Zhang, Xiaoping Liu, Boris Striepen, Jan R Mead, Gregory D Cuny and Lizbeth Hedstrom

Bioorganic & Medicinal Chemistry Letters, Vol.23(4), pp.1004-1007

02/15/2013

DOI: https://doi.org/10.1016/j.bmcl.2012.12.037

PMCID: PMC3557747

PMID: 23324406

Abstract

Cryptosporidiosis

IMPDH

Antiparasitic

IMP dehydrogenase

Biochemistry

Parasitology

Pharmaceuticals

Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5′-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure–activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented.

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Files and links (1)

url

Phthalazinone Inhibitors of Inosine-5’-Monophosphate Dehydrogenase from Cryptosporidium parvumView

Published (Version of record) Open

Metrics

32 Record Views

See more details

Details

Title: Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum
Creators: Corey R Johnson (Author) - Department of Chemistry, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, United States
Suresh Kumar Gorla (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, United States
Mandapati Kavitha (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, United States
Minjia Zhang (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, United States
Xiaoping Liu (Author) - Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, United States
Boris Striepen (Author) - Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, United States
Jan R Mead (Author) - Atlanta VA Medical Center and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, United States
Gregory D Cuny (Author) - Laboratory for Drug Discovery in Neurodegeneration, Brigham & Women’s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, United States
Lizbeth Hedstrom (Author) - Department of Chemistry, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, United States
Publication Details: Bioorganic & Medicinal Chemistry Letters, Vol.23(4), pp.1004-1007
Publisher: Elsevier Ltd
Identifiers: 9923957901101921
Academic Unit: Department of Chemistry; Department of Biology
Language: English
Resource Type: Journal article

Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum

Abstract

UN Sustainable Development Goals (SDGs)

Files and links (1)

Metrics

Details

Brandeis University Social media