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Letter

Discovery of 1,4-Didydroxy-2-naphthoate Prenyltransferase Inhibitors: New Drug Leads for Multidrug-Resistant Gram-Positive Pathogens

Michio Kurosu,* Prabagaran Narayanasamy, Kallolmay Biswas, Rakesh Dhiman, and Dean C. Crick*

Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1682 Campus Delivery, Fort Collins, Colorado 80523-1682

J. Med. Chem., 2007, 50 (17), pp 3973–3975

DOI: 10.1021/jm070638m

Publication Date (Web): July 21, 2007

To whom correspondence should be addressed. For M.K.: phone, 970-491-7628; fax, 970-491-1815; e-mail, michio.kurosu@colostate.edu. For D.C.C.: phone, 970-491-3308; fax, 970-491-1815; e-mail, dean.crick@ colostate.edu.

Abstract

Since utilization of menaquinone in the electron transport system is a characteristic of Gram-positive organisms, the 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) inhibitors 1a and 2a act as selective antibacterial agents against organisms such as methicillin-resistant Stapylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), and Mycobacterium spp. Growth of drug-resistant Gram-positive organisms was sensitive to the MenA inhibitors, indicating that menaquinone synthesis is a valid new drug target in Gram-positive organisms.

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