ABSTRACT
Leishmaniasis is a protozoan tropical infection that is estimated to be more than 0.3 million new cases occur annually worldwide. A novel phenolic compound, cultratin A (1), was isolated as a leishmanicidal constituent from the timber of Dalbergia cultrata, along with three known neoflavanoids (2, 3, 4), two benzofurans (5, 6), and two phenolic compounds (7, 8). Their structures were determined using spectral methods. Among them, a new compound (1) and 4-(S)-methoxydalbergione (2) showed effective leishmanicidal activities (IC50: 2.0 and 2.6 µM, respectively), while compound 8 showed moderate activity (IC50: 11 µM). The cytotoxicity of compounds 1 and 2 was also weaker than that of the other compounds.
Subject(s)
Antiprotozoal Agents , Benzofurans , Dalbergia , Leishmaniasis , Antiprotozoal Agents/pharmacology , Humans , Leishmaniasis/drug therapy , Phenols/pharmacology , Phenols/therapeutic useABSTRACT
A methanol extract of the wood of Diospyros burmanica, collected in Burma (Myanmar), was found to exhibit significant activity against Leishmania major. Subsequent chromatographically resolved fractionation led to the isolation of three novel bisnaphthoquinone analogues, burmanin A, B, and C (1-3), together with nine known compounds (4-12). The structure of 1 was confirmed by X-ray crystallography, and those of 2 and 3 by spectroscopic techniques, including 1D and 2D NMR. The inhibitory activities of the isolates were evaluated against the promastigote forms of Leishmania major and the murine macrophage-like cell line, RAW264.7.
Subject(s)
Antiprotozoal Agents/pharmacology , Diospyros/chemistry , Leishmania major/drug effects , Naphthols/pharmacology , Naphthoquinones/pharmacology , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Cell Survival/drug effects , Cells, Cultured , Crystallography, X-Ray , Dose-Response Relationship, Drug , Leishmania major/metabolism , Mice , Models, Molecular , Molecular Structure , Myanmar , Naphthols/chemistry , Naphthols/isolation & purification , Naphthoquinones/chemistry , Naphthoquinones/isolation & purification , Parasitic Sensitivity Tests , Plant Extracts/chemistry , Stereoisomerism , Structure-Activity Relationship , Wood/chemistryABSTRACT
A methanol extract of the wood of Cordia fragrantissima, collected in Burma (Myanmar), was found to exhibit significant activity against Leishmania major. Bioassay-guided fractionation of this extract using several chromatographic techniques afforded three new compounds (1-3) and five known compounds (4-8). The structures of the new compounds were revealed on the basis of spectroscopic data interpretation and by X-ray crystallographic analysis. Interestingly, the new compounds, despite the presence of asymmetric carbons, were found to be racemates. The activities of the isolates from C. fragrantissima and several derivatives were evaluated against the promastigote forms of Leishmania major, L. panamensis, and L. guyanensis.
Subject(s)
Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/pharmacology , Cordia/chemistry , Hydroquinones/isolation & purification , Hydroquinones/pharmacology , Leishmania/drug effects , Plants, Medicinal/chemistry , Animals , Antiprotozoal Agents/chemistry , Crystallography, X-Ray , Hydroquinones/chemistry , Leishmania/growth & development , Molecular Conformation , Molecular Structure , Myanmar , Parasitic Sensitivity TestsABSTRACT
Seventy-five Myanmar timber extracts belonging to 27 families were examined for their leishmanicidal activities. Some timber extracts had significant leishmanicidal activity, especially extracts of Millettia pendula, which exhibited the most potent activity (MLC 3.1 microg/ml, MIC 1.6 microg/ml). Other timber extracts showing potent activity included those from Cedrela serrata, Cedrela toona, Cordia fragrantissima, Calophyllum kunstleri, Dalbergia cultrate, Grevillea robusta, Haplophragma adenophyllum, Michelia champaca, and Tectona grandis. From a literature search for reports on the chemical constituents of these plants, most constituents were found to be quinone derivatives or other compounds with unsaturated carbonyl groups.
