Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH

Sivapriya Kirubakaran; Suresh Kumar Gorla; Lisa Sharling; Minjia Zhang; Xiaoping Liu; Soumya S Ray; Iain S MacPherson; Boris Striepen; Lizbeth Hedstrom; Gregory D Cuny

doi:10.1016/j.bmcl.2012.01.029

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Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH

Journal article

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Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH

Sivapriya Kirubakaran, Suresh Kumar Gorla, Lisa Sharling, Minjia Zhang, Xiaoping Liu, Soumya S Ray, Iain S MacPherson, Boris Striepen, Lizbeth Hedstrom and Gregory D Cuny

Bioorganic & Medicinal Chemistry Letters, Vol.22(5), pp.1985-1988

03/01/2012

DOI: https://doi.org/10.1016/j.bmcl.2012.01.029

PMCID: PMC3289519

PMID: 22310229

Abstract

Cryptosporidium

Benzimidazole

Parasite

Protozoan

Inhibitor

Structure–activity relationship

Inosine 5′-monophosphate dehydrogenase (IMPDH)

Biochemistry

Parasitology

Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure–activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.

UN Sustainable Development Goals (SDGs)

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

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Title: Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH
Creators: Sivapriya Kirubakaran (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, USA
Suresh Kumar Gorla (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, USA
Lisa Sharling (Author) - Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA
Minjia Zhang (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, USA
Xiaoping Liu (Author) - Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA
Soumya S Ray (Author) - Center for Neurologic Diseases, Department of Neurology, Brigham & Women’s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
Iain S MacPherson (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, USA
Boris Striepen (Author) - Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USA
Lizbeth Hedstrom (Author) - Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, USA
Gregory D Cuny (Author) - Laboratory for Drug Discovery in Neurodegeneration, Brigham & Women’s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
Publication Details: Bioorganic & Medicinal Chemistry Letters, Vol.22(5), pp.1985-1988
Publisher: Elsevier Ltd
Identifiers: 9923958389701921
Academic Unit: Department of Chemistry; Department of Biology
Language: English
Resource Type: Journal article

Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH

Abstract

UN Sustainable Development Goals (SDGs)

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