ABSTRACT
This is a comparative study on the intraspecific chemical variability of Aristolochia cordigera species, collected in two different regions of Brazil, Biome Cerrado (semiarid) and Biome Amazônia (coastal). The use of GC-MS and statistical methods led to the identification of 56 compounds. A higher percentage of palmitone and germacrene-D in the hexanes extracts of the leaves of plants from these respective biomes was observed. Phytochemical studies on the extracts led to the isolation and identification of 19 known compounds, including lignans, neolignans, aristolochic acids, indole-ß-carboline, and indole alkaloids. In addition, two new indole alkaloids, 3,4-dihydro-hyrtiosulawesine and 6-O-(ß-glucopyranosyl)hyrtiosulawesine, were isolated and a new neolignan, cis-eupomatenoid-7, was obtained in a mixture with its known isomer eupomatenoid-7. Their structures were determined by spectroscopic methods, mainly by 1D- and 2D-NMR. The occurrence of indole alkaloids is being described for the first time in the Aristolochiaceae family. Moreover, the in vitro susceptibility of intracellular amastigote and promastigote forms of Leishmania amazonensis to the alkaloids and eupomatenoid-7 were evaluated. This neolignan exhibited low activity against promastigotes (IC50 = 46 µM), while the alkaloids did not show inhibitory activity. The new alkaloid 6-O-(ß-glucopyranosyl)hyrtiosulawesine exhibited activity in the low micromolar range against Plasmodium falciparum, with an IC50 value of 5 µM and a selectivity index higher than 50.
Subject(s)
Antiprotozoal Agents/pharmacology , Aristolochia/chemistry , Cytotoxins/pharmacology , Indole Alkaloids/pharmacology , Lignans/pharmacology , Plant Extracts/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Brazil , Cell Line, Tumor , Cytotoxins/chemistry , Cytotoxins/isolation & purification , Gas Chromatography-Mass Spectrometry , Humans , Indole Alkaloids/chemistry , Indole Alkaloids/isolation & purification , Leishmania/drug effects , Lignans/chemistry , Lignans/isolation & purification , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plasmodium falciparum/drug effectsABSTRACT
Root extracts of Holostylis reniformis (Aristolochiaceae) yielded three new natural sesquiterpenes, a sesquiterpene with an unusual carbon skeleton, 4,5-seco-guaiane (7-epi-11-hydroxychabrolidione A, 1), a nine-membered lactone with new carbon skeleton (holostylactone, 2), and a new megastigmane [(6S,7E)-6,9-dihydroxy-10-(2'-hydroxy-ethoxy)-4,7-megastigmadien-3-one, 3], together with bulnesol and sitosterol-3-O-β-D-glucopyranoside. The structures of these compounds were determined by spectroscopic analyses and B3LYP/STO-3G** theoretical studies.
Subject(s)
Aristolochiaceae/chemistry , Lactones , Sesquiterpenes, Guaiane/chemistry , Sesquiterpenes , Lactones/chemistry , Lactones/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/chemistry , Plant Roots/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Sesquiterpenes, Guaiane/isolation & purificationABSTRACT
Holostylis reniformis biosynthesizes 8-8' linked lignans without 9,9'-oxygenation. To elucidate the biosynthetic pathways to these lignans, the reputed precursors [U-(14)C]phenylalanine, [9-(3)H(1)]coniferyl alcohol, and [9-(3)H(1)]isoeugenol were administered to roots of the plant, which led to the incorporation of (3)H and (14)C into ten 2,7' linked-lignans (aryltetralone lignans) and two 7,7'-epoxylignans (furan lignans). These administration experiments demonstrated that the lignans were propenylphenol-derived and that H. reniformis can exhibit regioselective control over radical-radical coupling (via isoeugenol radicals). Regiospecific control over propenylphenol-derived lignan biosynthesis was observed, together with diastereoselective control of C2-C7' bond formation for the aryltetralone lignans (7'R). These experiments provide evidence that isoeugenol is a biosynthetic intermediate to the aryltetralone and furan lignans.
Subject(s)
Antimalarials/metabolism , Aristolochiaceae/metabolism , Lignans/biosynthesis , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, UltravioletABSTRACT
Extracts from Holostylis reniformis were tested in vivo against Plasmodium berghei and in vitro against a chloroquine-resistant strain of Plasmodium falciparum. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7'R,8S,8'S)-3',4'-methylenedioxy-4,5-dimethoxy-2,7'-cyclolignan-7-one, were isolated and tested in vitro against P. falciparum. The three most active lignans showed 50% inhibitor concentrations of < or =0.32 microM. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.
Subject(s)
Antimalarials/pharmacology , Aristolochiaceae/chemistry , Lignans/pharmacology , Tetralones/pharmacology , Animals , Antimalarials/isolation & purification , Cell Line, Tumor , Chromatography, High Pressure Liquid , Circular Dichroism , Formazans/metabolism , Humans , Inhibitory Concentration 50 , Lignans/chemistry , Mice , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Parasitemia/drug therapy , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Roots/chemistry , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Spectrophotometry, Ultraviolet , Tetralones/chemistryABSTRACT
Aryltetralol and aryltetralone lignans were isolated from the hexane extracts of the roots of Holostylis reniformis. Their structures were determined by spectroscopic methods and chemical transformations.
Subject(s)
Aristolochiaceae/chemistry , Lignans/chemistry , Plant Roots/chemistry , Tetralones/chemistry , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular StructureABSTRACT
Aryltetralone lignans and two 7,8-seco-lignans were isolated from the acetone and hexane extracts of the roots of Holostylis reniformis, together with (-)-galbacin. Their structures were determined by spectroscopic methods.