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Antimicrobial Agents and Chemotherapy, March 2008, p. 1162-1166, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.00968-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antimycobacterial Activity and Mechanism of Action of NAS-91{triangledown}

Paul Gratraud,1 Namita Surolia,3 Gurdyal S. Besra,4 Avadhesha Surolia,5,6 and Laurent Kremer1,2*

Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier II et I, CNRS, UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France,1 INSERM, DIMNP, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France,2 Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India,3 School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom,4 Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India,5 National Institute of Immunology, New Delhi 110067, India6

Received 26 July 2007/ Returned for modification 21 August 2007/ Accepted 5 December 2007

The antimalarial agents NAS-91 and NAS-21 were found to express potent antimycobacterial activity, NAS-91 being more active than NAS-21. They partially inhibited mycolic acid biosynthesis and profoundly altered oleic acid production. The development of a cell-free assay for {Delta}9-desaturase activity allowed direct demonstration of the inhibition of oleic acid biosynthesis by these compounds.

* Corresponding author. Present address: CNRS UMR 5235, Montpellier, France. Phone: 33 4 67 14 33 81. Fax: 33 4 67 14 42 86. E-mail: laurent.kremer{at}univ-montp2.fr

{triangledown} Published ahead of print on 17 December 2007.

Antimicrobial Agents and Chemotherapy, March 2008, p. 1162-1166, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.00968-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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