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Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design.

ABSTRACT: The relaxed complex scheme, a virtual-screening methodology that accounts for protein receptor flexibility, was used to identify a low-micromolar, non-bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, we also found that several predicted farnesyl diphosphate synthase inhibitors were low-micromolar inhibitors of undecaprenyl diphosphate synthase. These results are of interest because farnesyl diphosphate synthase inhibitors are being pursued as both anti-infective and anticancer agents, and undecaprenyl diphosphate synthase inhibitors are antibacterial drug leads.

SUBMITTER: Durrant JD

PROVIDER: S-EPMC3155669 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design.

Durrant Jacob D JD Cao Rong R Gorfe Alemayehu A AA Zhu Wei W Li Jikun J Sankovsky Anna A Oldfield Eric E McCammon J Andrew JA

Chemical biology & drug design 20110803 3

The relaxed complex scheme, a virtual-screening methodology that accounts for protein receptor flexibility, was used to identify a low-micromolar, non-bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, we also found that several predicted farnesyl diphosphate synthase inhibitors were low-micromolar inhibitors of undecaprenyl diphosphate synthase. These results are of interest because farnesyl diphosphate synthase inhibitors are being pursued as both anti-infective and an ...[more]

PMID: 21696546

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