Synthesis and anti-Trypanosoma cruzi activity of β-lapachone analogues.

The available chemotherapy for Chagas disease, caused by Trypanosoma cruzi, is unsatisfactory; therefore, there is an intense effort to find new drugs for the treatment of this disease. In our laboratory, we have analyzed the effect on bloodstream trypomastigotes of 16 new naphthoquinone analogues of β-lapachone modified in the pyran ring, aiming to find a new prototype with high trypanocidal activity. The new compounds presented a broad spectrum of activity, and five of them presented IC(50)/24 h in the range of 22-63 μM, whereas β-lapachone had a higher value of 391.

1,2-Dihydr-oxy-2-(3-methyl-but-2-en-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylic acid monohydrate.

The title compound, C(15)H(16)O(5)·H(2)O, is an inter-mediate of the Hooker oxidation reaction, used for the synthesis of 2-hydr-oxy-3-(2-methyl-prop-1-en-yl)naphthalene-1,4-dione (nor-lapachol). The packing in the crystal structure is arranged by an O-H⋯O hydrogen-bonded network along the [100] and [010] directions. Each organic mol-ecule is linked to four other mol-ecules via the hydr-oxy groups.

The trypanocidal activity of naphthoquinones: a review.

Naphthoquinones are compounds present in several families of higher plants. Their molecular structures confer redox properties, and they are involved in multiple biological oxidative processes. In folk medicine, especially among Indian populations, plants containing naphthoquinones have been employed for the treatment of various diseases.

Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation.

In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, alpha-iodinated naphthofuranquinone (NPPN-3223), beta-iodinated naphthofuranquinone (NPPN-3222) and beta-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate-lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced to their seminaphthofuranquinone radical by the liver NADPH-P450 reductase system, as detected by ESR measurements.

Activities of naphthoquinones against Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae), vector of dengue and Biomphalaria glabrata (Say, 1818), intermediate host of Schistosoma mansoni.

Larvicidal (against Aedes aegypti Linnaeus, 1762) and molluscicidal (against Biomphalaria glabrata Say, 1818) activities of several natural and synthetic naphthoquinones were measured, with significant results. The best larvicidal compound is 3-bromojuglone, while the better molluscicides are 2-bromo- and 3-bromo-5-acetoxy-1,4-naphthoquinones together with the 3-bromo-5-methoxy derivative. The present results reinforce the potential use of substituted hydroxyquinones, their salts and halogenated quinones as very promising compounds against 4th instar larves of Aedes aegypti, the vector of dengue and against adult snail of Biomphalaria glabrata.

Ex vivo activities of beta-lapachone and alpha-lapachone on macrophages: a quantitative pharmacological analysis based on amperometric monitoring of oxidative bursts by single cells.

ARTIFICIAL SYNAPSES FOR FEMTOMOLAR DETECTION: Amperometry at platinized carbon fibre electrodes has been used to unravel the complexity of beta-lapachone's effects on cellular oxidative stress. Alpha-lapachone, the pharmacologically inactive para-quinone isomer, did not display such characteristics, but over longer incubation periods both quinones induced apoptosis. The observed effects were interpreted in terms of two mechanisms involving opposite reactivities of quinones in living cells.

Inner reorganization during the radical-biradical transition in a nor-beta-lapachone derivative possessing two redox centers.

In this work, the electrochemical behaviour of an antitumoral nitro o-quinone derivative obtained from 3-bromo-nor-beta-lapachone was studied. Cyclic voltammetric experiments, in acetonitrile solution, revealed that both quinone and nitro functions are reduced independently as quasi-reversible one-electron transfer processes in this order. Depending on the reduction potential, a radical anion or a biradical dianion is obtained.

Tabebuia avellanedae naphthoquinones: activity against methicillin-resistant staphylococcal strains, cytotoxic activity and in vivo dermal irritability analysis.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococcus infections are a worldwide concern. Currently, these isolates have also shown resistance to vancomycin, the last therapy used in these cases. It has been observed that quinones and other related compounds exhibit antibacterial activity.

Synthesis of naphthofuranquinones with activity against Trypanosoma cruzi.

Four new naphthofuranquinones, obtained from 2-hydroxy-3-allyl-naphthoquinone (1) and nor-lapachol (2), have their structures established by physical and X-ray analysis and their activity evaluated against Trypanosoma cruzi. Compounds 3 and 4 were obtained by addition of iodine to 1 followed by cyclization generating a furan ring. Compound 5 was obtained through the acid-catalyzed reaction by dissolution of 1 in sulfuric acid.

A trypanocidal phenazine derived from beta-lapachone.

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.