Biologically active terpenoids from Bolivian medicinal plants

Abstract: Pseudo-guaianolides represent a large group of sesquiterpene lactones exhibiting significant cytotoxic and anti-inflammatory activities. Their biological activities are due to a 훼-methylene-훾-lactone unit in their chemical structure, which reacts with free sulfhydryl groups of free cysteine via a Michael-addition. Damsin is a major pseudo guaianolide found in Ambrosia arborescens Mill., a plant distributed in Andes of Bolivia, Peru, Ecuador and Colombia. The aerial parts of this plant are used in traditional medicine against Abortion, menstrual retardation, rheumatic pain. The overall aim of this thesis was to obtain biological active semi-synthetic pseudo guaianolides from Ambrosia arborescens Mill and triterpenes from Bolivian Highlands plants based on Claisen Schmidt condensation conditions.Paper I Outlines the HPLC evaluation of damsin and coronopilin isolated from Ambrosia arborescens Mill in the plant, and their effects of inhibition of pro-inflammatory IL-6 and MCP-1expression in human skin cells though of NF-κB inhibition.Paper II describes the evaluation of selective cytotoxicity of 23-α-methylene-γ-lactones based on damsin in normal breast epithelial MCF-10A cells and breast cancer JIMT-1 cells, where the IC50 values were found to depend strongly on the overall structure. Paper III refers to semi-synthesis of new derivatives preserving the α-methylene-γ-lactone unit in which Claisen Schmidt condensation products such as (E)-3-benzylidendamsin derivatives were found to be more potent in the JIMT-1 cancer cells compared to the MCF-10A normal like cells.Paper IV describes the oleanolic acid determination in Bolivian highland plants such as Tetraglochin cristatum, Lampaya castellani, Junellia seriphioides, Baccharis tola, Polylepis tomentella, P. hieronyni, P. besseri and Satureja boliviana, according of our results these plants can be a potential natural source of oleanolic acid since this compound has several applications.Paper V present the obtention of oleanolic acid derivatives via Claisen Schmidt condensation and the evaluation of cytotoxicity of four sapogenins from Chenopodium quinoa.Paper VI refer to acute anti-inflammatory activity evaluation of oleanolic acid 1, methyl oleanate 2, hederagenin 3 and phytolaccagenic acid 4 sapogenins from Chenopodium quinoa in two murine models: The carrageenan-induced paw edema, and the croton-induced ear edema. the extract shows anti-inflammatory activity significant in ear edema model than the compounds, while in the paw edema model the isolated compounds show a significant anti-inflammatory activity than the extract.