Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design
Jacob D Durrant1, Rong Cao, Alemayehu A Gorfe
1Department of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Drive, Mail Code 0365, La Jolla, CA 92093, USA. jdurrant@ucsd.edu
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.
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