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Antimicrobial Agents and Chemotherapy, February 2005, p. 808-812, Vol. 49, No. 2
0066-4804/05/$08.00+0 doi:10.1128/AAC.49.2.808-812.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
U R008, Pathogénie des Trypanosomatidés, Centre IRD de Montpellier, Montpellier, France,1 Department of Biochemistry, Faculty of Pharmacy, and Institute of Cellular and Molecular Biology, University of Porto, Porto, Portugal2
Received 31 August 2004/ Returned for modification 12 October 2004/ Accepted 18 October 2004
Our study represents the first report demonstrating the antileishmanial activity of nicotinamide (NAm), a form of vitamin B3. A 5 mM concentration of NAm significantly inhibited the intracellular growth of Leishmania amastigotes and the NAD-dependent deacetylase activity carried by parasites overexpressing Leishmania major SIR2 (LmSIR2). However, the transgenic parasites were as susceptible as the wild-type parasites to NAm-induced cell growth arrest. Therefore, we conclude that NAm inhibits leishmanial growth and that overexpression of LmSIR2 does not overcome this inhibition. The mechanism of the inhibition is not defined but may include other in vivo targets. NAm may thus represent a new antileishmanial agent which could potentially be used in combination with other drugs during therapy.
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