ABSTRACT
In the study, we have examined the antitumor and antimicrobial activities of the methanol extract, the fractions, a fraction of total alkaloids and two alkaloids isolated from the stem of Erythroxylum caatingae Plowman. All test fractions, except the hexane fractions, showed antimicrobial activity on gram-positive bacteria and fungi. The acetate: methanol (95:5), acetate, chloroform and hexane fractions show the highest cytotoxicity activity against the NCI-H292, HEp-2 and K562 cell lines using MTT. The absence of hemolysis in the erythrocytes of mice was observed in these fractions and 6ß-Benzoyloxy-3α-(3,4,5- trimethoxybenzoyloxy) tropane (catuabine B). Staining with Annexin V-FITC and JC-1 was used to verify the mechanism of action of the compounds of E. caatingae that showed cytotoxicity less than 30 µg/mL in leukemic cells. After 48 h of incubation, we observed that the acetate: methanol (95:5), acetate, and chloroform fractions, as well as the catuabine B, increased in the number of cells in early apoptosis, from 53.0 to 74.8%. An analysis of the potential of the mitochondrial membrane by incorporation of JC-1 showed that most cells during incubation of the acetate: methanol (95:5) and acetate fractions (63.85 and 59.2%) were stained, suggesting the involvement of an intrinsic pathway of apoptosis.
Subject(s)
Anti-Infective Agents/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Erythroxylaceae/metabolism , Plant Stems/metabolism , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Anti-Infective Agents/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival , Drug Discovery , Erythrocytes/drug effects , Female , Fungi/drug effects , Gram-Positive Bacteria/drug effects , Hemolysis/drug effects , Hep G2 Cells , Humans , Leukemia/drug therapy , Membrane Potential, Mitochondrial/drug effects , Mice , Microbial Sensitivity Tests , Mitochondrial Membranes/drug effects , Plant Extracts/pharmacologyABSTRACT
Three tropane alkaloids, 1-3, were isolated from Erythroxylum caatingae, i.e., 6ß-benzoyloxy-3α-[(4-hydroxy-3,5-dimethoxybenzoyl)oxy]tropane (1), a new tropane alkaloid, along with the known alkaloids 3α,6ß-dibenzoyloxytropane (2) and 6ß-benzoyloxy-3α-[(3,4,5-trimethoxybenzoyl)oxy]tropane (catuabine B; 3). Their structures were determined by 2D- ((1) H and (13) C) NMR. By LC/ESI-MS/MS analysis of the fractions of alkaloids 1-3, it was possible to detect five more alkaloids, 4-8, two of these, 4 and 8, possibly being new natural products. X-Ray crystallography of the chloride derivate of 1, i.e., 6ß-benzoyloxy-3α-(4-hydroxy-3,5-dimethoxybenzoyloxy)tropane hydrochloride (1a) confirmed the structure of 1. Cytotoxicity was tested against the cell lines HEp-2, NCI-H292, and KB for the MeOH extract and alkaloid 3, and antitumor activity was tested against Sarcoma 180 only for the MeOH extract.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Erythroxylaceae/chemistry , Tropanes/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/toxicity , Cell Line, Tumor , Crystallography, X-Ray , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , Plant Stems/chemistry , Tropanes/isolation & purification , Tropanes/toxicityABSTRACT
Erythroxylum, the most representative genus of the Erythroxylaceae family, presents tropane alkaloids as main constituents. This class of compounds greatly contributes to the chemotaxonomic characterization of plants of this genus, and it has important medical uses and shows toxic effects. This review describes 186 tropane alkaloids in the 35 species of Erythroxylum distributed worldwide. In addition, a compilation of their (13)C-NMR spectral data is presented.
