Planta Med 2008; 74 - PG26
DOI: 10.1055/s-0028-1084779

In vitro antimycobacterial activity evaluation of (-)-Cubebin and its semi-synthetic derivatives against three species of Mycobacteria

CHG Martins 1, DN Sato 2, FG Pavan 2, LN Andrade 2, AC Pereira 1, TNC Bianco 1, TC Carvalho 1, JK Bastos 3, AHC Vinholis 1, R Silva 1, WR Cunha 1, AA Da Silva Filho 1, MLA Silva 1
  • 1Universidade de Franca, Av. Dr. Armando Salles de Oliveira, 201, CEP: 14404–600– Franca – SP – Brazil
  • 2Instituto Adolfo Lutz de Ribeirão Preto-SP
  • 3Faculdade de Ciências Farmacêuticas de Ribeirão Preto – USP, Av. do Café S/N – Ribeirão Preto – São Paulo-Brazil

The increase in the case rates of drug resistant tuberculosis and nontuberculous mycobacterial infections have brought renewed urgency to the development of new treatment for mycobacterial infections [1]. In the last decade there has been intensification in the search of antimycobacterial compounds from natural sources [1,2]. The aim of this work was to evaluate the antimycobacterial activity of (-)-cubebin and some of its semi-synthetic derivatives. (-)-Cubebin (1) was obtained from seeds of Piper cubeba and its semi-synthetic derivatives (-)-hinokinin (2), (-)–O-acetyl-cubebin (3), (-)–O-methyl-cubebin (3), (-)-O-(N,N-dimethylaminoethyl)-cubebin (4), and (-)-6,6'-dinitrohinokinin (5) were obtained by synthetic procedures, including oxidation and addition of acetyl or methyl groups to the lactolic hydroxyl group of (-)-cubebin [2]. The MIC was determined using the Resazurin Microplate Assay (RMA)[3]. The MIC values of the (-)-cubebin compounds ranged from 62.5 to 1000µg/mL for M. tuberculosis and M. kansasii. (-)-Hinokinin stood out by displaying a promising MIC of 62.5µg/mL. The (-)-cubebin compounds were active against M. tuberculosis and M. kansasii (ATCC 12478), but inactive against M. avium (ATCC 12478). Further studies will be undertaken to determine the cellular cytotoxicity and intracellular antimycobacterial activity of these compounds.

Acknowledgements: To FAPESP (Process 04/13368–7, 03/01475–0, 98/14956–7 and 05/01550–8), (CAPES), CNPq (Process 301139/2007–5 and 119832/2007–0) for financial support.

References: 1. a)Espinal, M. A. et al. N. Engl. J. Med., 344, 1294–1303, 2001.b)Perri, G. D.; Bonora, S. J. Antimicrobial Chem., 54, 593–602, 2004; c)Inderlied, C.B. et al. Clin. Microbiol. Rev., 6(3), 266–310, 1993.

2. a)Souza, G.H.B.,et al. (2004) Il Farm. 59: 55–61 b) Souza, V.A. et al. (2005) Bioorg Med Chem. 15:303–307.

3. Palomino, J. C. et al. (2002) Antimicrob. Agents Chemother. 46: 2720–2722.