In vitro andin vivo Leishmanicidal activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol)

Antileishmanial activity of lapachol analogues

“…Atovaquone, a hydroxynaphtoquinone, showed to have a concentration-dependent in vitro activity against L. infantum (Jernigan et al 1996), while the in vivo activity in a murine model remained low (Murray et al 1996, Cauchetier et al 2000. Lapachol was effective in vitro against intracellular amastigotes of L. braziliensis, whereas in a hamster model, it was unable to prevent lesions induced by the infection (Teixeira et al 2001). It was suggested that lapachol could be transformed in vivo into an inactive metabolite (Teixeira et al 2001).…”

“…Lapachol was effective in vitro against intracellular amastigotes of L. braziliensis, whereas in a hamster model, it was unable to prevent lesions induced by the infection (Teixeira et al 2001). It was suggested that lapachol could be transformed in vivo into an inactive metabolite (Teixeira et al 2001). Apart from these studies, lapachol and other quinones are known to possess antitumor, antibiotic, antimalarial, anti-inflammatory, and anti-ulcer activities (Subramanian et al 1998, reviewed in De Moura et al 2001.…”

Synthesis of new aldehyde derivatives from β-lapachone and nor-β-lapachone

“…A central feature of ortho and para-quinonoid based cytotoxins is their ability to generate semi-quinone radicals by bioreduction, which then accelerates intracellular hypoxic conditions. 1,2 The drug arsenal for fighting against tropical diseases includes many natural and synthetic naphthoquinone derivatives, which have been studied extensively due to their abilities to interfere with the bio-activities of enzymes known as topoisomerases, a group of enzymes that are critical for DNA replication in cells. In addition, naphthoquinones have been shown to induce what are known as 'reactive oxygen species' that can cause damage to cells.…”

“…is due to their interaction with the mitochondrial respiratory chain of the parasites. 2 This observation led Fieser and collaborators in the 1940´s to start an extensive search for new quinones for use in malaria chemotherapy. 2 Subsequently, quinones have been studied for antitumor, 2 trypanocidal, 2 molluscicidal, 1 leiscmanicidal, 2 anti-inflammatory 3 and antifungal 4 activities.…”

“…2 This observation led Fieser and collaborators in the 1940´s to start an extensive search for new quinones for use in malaria chemotherapy. 2 Subsequently, quinones have been studied for antitumor, 2 trypanocidal, 2 molluscicidal, 1 leiscmanicidal, 2 anti-inflammatory 3 and antifungal 4 activities. Among significant biological active naphthoquinones are atovaquone 1, 5,6 a coenzyme Q analogue, which inhibits selectively P. Vivae by affecting its mitocondrial electron transport and lapachol 2, a versatile biologically active compound, present in the heartwood of several Tabebuia species from Central and South America, especially Tabebuia avellanedae Lorentz ex Grised (Bignoniaceae) 7, , 8 9 , see Figure 1.…”