A Trypanocidal Phenazine Derived from β-Lapachone

Abstract

An intensive effort has been directed toward finding alternative drugs for treatment of Chagas' disease, caused by Trypanosoma cruzi, and prophylaxis of blood in endemic areas. Our research comprises the synthesis and trypanocidal screening of derivatives from naphthoquinones. Herein a new phenazine, obtained from the reaction of beta-lapachone with aniline, has its structure established by physical data and X-ray analysis. It was 9 times more active against T. cruzi trypomastigotes than crystal violet.

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

“…In this context, some natural products obtained from plant extracts or their derivatives, such as quinones, alkaloids, terpenes, and phenolic derivatives, have been proposed for leishmaniasis chemotherapy (9). Recently, we reported evidence that quinone derivatives exhibited promising properties against protozoan parasites, such as Trypanosoma cruzi (10)(11)(12)(13)(14), Leishmania (Viannia) braziliensis, and Leishmania (Leishmania) amazonensis (15). These compounds can be isolated from Bignoniaceae or Verbenaceae trees, and their antimicrobial properties have been well established (16).…”

Antileishmanial and Trypanocidal Activities of Extracts and Aporphine Alkaloids Isolated from Monodora Genus (Annonaceae)

“…Indeed, some of the oxoaporphines which differ slightly in chemical structure showed clear differences in activity in this study. For example, (+)-Listeferine (8; Figure 1) which is a demethylated derivative of (+)-reomeroline (9), is about twice more active than the latter against L. donovani; an observation that demethylation at R 3 led to increased antiprotozoal activity of the latter.…”

“…In the past few years, the interest in natural products as a potential source for the treatment of parasitic diseases has increased [5][6][7][8]. Traditionally, plants have been used for the treatment of protozoan diseases and phytotherapy has over the years received considerable attention in the search for alternative compounds with antiparasitic activity [9,10]. In our search for chemical agents from tropical medicinal plants for the treatment of Leishmaniasis and Trypanosomiasis, we evaluated eleven compounds, isolated from Monodora crispata and Monodora brevipes together with the serially extracted organic solvent extracts of the two plants against Leishmania donovani promastigotes and Trypanosoma brucei brucei trypomastigotes.…”

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

“…Lastly, suksdorfin (96), another natural compound isolated from the fruit of Lomatium suksdorfii, exhibits a significant anti-HIV activity as it inhibits the viral replication in the T-cell line with an EC50 in the 2.5 µM range [116] (Figure 8). In a similar approach, Wang et al [118] have reported a new one-pot two-step tandem synthesis of highly functionalized benzo[a]pyrano [2,3- [119][120][121]. This reaction was achieved by the simple condensation of 2-hydroxynaphthalene-1,4-dione (104), diamines 105, aldehydes 107 and malonitrile (108).…”

“…In a similar approach, Wang et al [118] have reported a new one-pot two-step tandem synthesis of highly functionalized benzo[a]pyrano [2,3- [119][120][121]. This reaction was achieved by the simple condensation of 2-hydroxynaphthalene-1,4-dione (104), diamines 105, aldehydes 107 and malonitrile (108).…”