Special Issue Reviews and Accounts ARKIVOC 2007 (ii) 145-171
6. Biosynthesis 7. Derivatives 8. Perspectives 1. Introduction Compounds having a quinone as the core system have promising biological activity. A central feature of ortho-and para-quinonoid based cytotoxins is their ability to generate semiquinone radicals by bioreduction, which then accelerates intracellular hypoxic conditions.1,2,3 The drug arsenal currently available for fighting against tropical diseases includes many natural and synthetic naphthoquinone derivatives which have been extensively studied due to their ability to interfere with the bio-activities of enzymes known as topoisomerases,3 a group of enzymes that are critical for DNA replication in cells. In addition, naphthoquinones have been shown to induce the so-called “reactive oxygen species” that can cause damage to cells.3 Since the pioneering work of Wendel4 in 1946, who demonstrated that certain naphthoquinones inhibit the growth of Plasmodium vivae, and the work of Fieser et al. in the 1940’s, an extensive search for new quinones for use in malaria chemotherapy has started.5 Subsequently, quinones have been studied for antitumor,6 trypanocidal,7 molluscicidal,8 leiscmanicidal,9 anti-inflammatory10 and antifungal11 activities. Lapachol 1 (Figure 1) was first isolated from Tabebuia avellanedae (Bignoniaceae) and in the years since the first review on lapachol, published in Portuguese in 2003 in Revista Brasiliera de Farmacia,12 there has been a rapid increase in the information available on lapachol.
2. Occurance Lapachol (1) has also been isolated from other families such as Verbenaceae, Proteaceae, Leguminosae, Sapotaceae, Scrophulariaceae, and Malvaceae (Table 1). Among the many significantly biologically active naphthoquinones, lapachol (1) is one of the most versatile biologically active compounds and its presence was sought and found later in several other species13-32 and different families as illustrated in Table 1.
2.1 Tabebuia avellanedae Lapachol (1) was first isolated by E. Paterno33 from Tabebuia avellanedae in 1882. Tabebuia avellanedae (Figure 2) is a tree from the Bignoniaceae family. Commonly know as "pau d'arco" (alternative name: Lapacho, Pau d'Arco; Taheebo) in Brazil, and its inner bark is used as an analgesic, anti-inflammatory, antineoplasic34 and diuretic by the local people in the north eastern parts of Brazil. Its anti-inflammatory, antimicrobial, and antineoplasic activities are cited in the
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