Antimycobacterial Activity of Natural and Semi-Synthetic Lignans

Tuberculosis is a severe infectious disease caused by mycobacteria belonging to the Mycobacterium tuberculosis complex. According to WHO, tuberculosis affects nearly 30% of the world’s population and is responsible for 3 million deaths worldwide each year, mainly in developing countries (Raviglione, 2003; WHO, 2003). The chemotherapy of tuberculosis has been based on the use of combined drug therapy with rifampicin, isoniazid, and pyrazinamide. However, the incorrect use and long drug administration, as well as the high cost and the countless side-effects have led people to abandon the treatment before being completely cured, leading to resistant bacilli (Timmins and Deretic, 2006; Hardna et al., 2001). In addition, the existence of drug-resistant tuberculosis reinforces the need to develop new safe and effective antimycobacterial drugs. Although several research programs have focused on various strategies to control tuberculosis, drug discovery has been one of the main areas of concentrated effort (Okunade and Elvin-Lewis, 2004; Raviglione, 2003; Collins and Franzblau, 1997). In the last decade there has been intensifi cation in the search for antibacterial compounds from natural sources, mainly from plants, which continue to be a major source of biologically active metabolites that may provide lead structures for the development of new drugs (Copp, 2003; Okunade and Elvin-Lewis, 2004; Da Silva Filho et al., 2004a, 2008a; Pontin et al., 2008). Lignans, one of the oldest classes of natural products, have attracted much interest over the years on account of their broad range of biological activities, including antileishmanial (Da Silva Filho et al., 2008b), trypanocidal (Da Silva Filho et al., 2004b; Souza et al., 2005), and anti-infl ammatory (Silva et al., 2005; Souza et al., 2004; Da Silva Filho et al., 2004c) activities. Cubebin, a dibenzylbutyrolactolic lignan, and its semi-synthetic derivatives have been investigated for their antiprotozoal and antibacterial activities (Andrade et al., 2009; Souza et al., 2005). Recently, it has been reported that dibenzylbutyrolactone lignans, obtained from cubebin, display signifi cant antibacterial activity against oral pathogens (Silva et al., 2007). Considering the antibacterial activity of dibenzylbutyrolactone lignans and as part of our works Antimycobacterial Activity of Natural and Semi-Synthetic Lignans Marcio Luis A. Silva*, Carlos H. G. Martins, Rodrigo Lucarini, Daisy N. Sato, Fernando R. Pavan, Nayara H. A. Freitas, Leonardo N. Andrade, Ana C. Pereira, Thais N. C. Bianco, Adriana H. C. Vinholis, Wilson R. Cunha, Jairo K. Bastos, Rosangela Silva, and Ademar A. da Silva Filho