Triazole-linked inhibitors of inosine monophosphate dehydrogenase from human and mycobacterium tuberculosis

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

The modular nature of nicotinamide adenine dinucleotide (NAD)-mimicking inosine monophsophate dehydrogenase (IMPDH) inhibitors has prompted us to investigate novel mycophenolic adenine dinucleotides (MAD) in which 1,2,3-triazole linkers were incorporated as isosteric replacements of the pyrophosphate linker. Synthesis and evaluation of these inhibitors led to identification of low nanomolar inhibitors of human IMPDH and more importantly the first potent inhibitor of IMPDH from Mycobacterium tuberculosis (mtIMPDH). Computational studies of these IMPDH enzymes helped rationalize the observed structure-activity relationships. Additionally, the first cloning, expression, purification and characterization of mtIMPDH is reported.

Original languageEnglish (US)
Pages (from-to)4768-4778
Number of pages11
JournalJournal of medicinal chemistry
Volume53
Issue number12
DOIs
StatePublished - Jun 24 2010

Fingerprint Dive into the research topics of 'Triazole-linked inhibitors of inosine monophosphate dehydrogenase from human and mycobacterium tuberculosis'. Together they form a unique fingerprint.

Cite this