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Terpenoid Plant Metabolites - Structural Characterization and Biological Importance

Maldonado, Eliana LU (2014)
Abstract (Swedish)
Popular Abstract in English

The secondary metabolites found in plants represent an extremely rich and limitless source of novel chemical diversity for drug discovery. In fact, some of the most important drugs currently in use today are derived from plants and they were discovered as a result of the study of medicinal plants used in traditional medicine. In this context, Bolivia is one of the most biological diverse countries of the world maintaining vast intact humid and dry forest ecosystems, which are the habitat of more than 20,000 species of higher plants. Due to the biodiversity and individuality of each geographical region, the medicinal plant knowledge is unique to the ethnical group living and working in these... (More)
Popular Abstract in English

The secondary metabolites found in plants represent an extremely rich and limitless source of novel chemical diversity for drug discovery. In fact, some of the most important drugs currently in use today are derived from plants and they were discovered as a result of the study of medicinal plants used in traditional medicine. In this context, Bolivia is one of the most biological diverse countries of the world maintaining vast intact humid and dry forest ecosystems, which are the habitat of more than 20,000 species of higher plants. Due to the biodiversity and individuality of each geographical region, the medicinal plant knowledge is unique to the ethnical group living and working in these regions and it is therefore essential to preserve them. The current renewed interest in natural products prompted us to study medicinal plants as source of bioactive compounds with anticancer or leishmanial activities.

In this thesis, medicinal plants growing at high altitudes were collected in Cochabamba, Bolivia, and their ethanol crude extracts screened for leishmanicidal activity. Kaunia lasiophthalma, Trixis antimenorrhoea and Lantana balansae showed high or moderate activity and were therefore chosen for detailed phytochemical and biological studies.

Kaunia lasiophthalma yielded two new eudesmane derivatives, a novel terpenoid, and several previously discovered sesquiterpenes and flavonoids. The anticancer activities of the isolated sesquiterpene lactones assayed in five brest-cancer cell lines was compared with the cytotoxicity in the normal-like epithelial cell line, MCF-10A. These biological results demostrate that all assayed compounds showed different levels of cytotoxicity and that the normal-like MCF-10A was the least sensitive to all compounds.

Trixis antimenorrhoea was found to be rich in terpenoids and flavonoids, which are interesting groups of natural products that have shown to exhibit several biological properties including leishmanicidal activity. T. antimenorrohea produced two new natural products, a novel nortrixane and a trixanolide derivative. The low yield of the novel nortrixane prevented further studies of this compound, while the new trixanolide exhibited high activity towards the two strains of Leishmania parasite used in this study. The lupane-type triterpernes and the flavonoids displayed different levels of activity.

From the bioactive extract of Lantana balansae several known secondary metabolites were isolated, structurally analyzed and their biological activity evaluated. As a result, the cyclopentenone fatty derivative and the two flavanones are new classes of secondary metabolites for the genus Lantana and flavonoids were found to be the major metabolites. The potent antileishmanial activity of 12 oxo-phytodienoic and flavonoids explain the significant activity of the crude extract of L. balansae.

In addition, structure elucidation of three novel macrocyclic monoterpene O glycosides isolated from the medicinal plant Parkinsonia aculeata was established by NMR and MS techniques.

In summary, this research project contributes to the chemical knowledge of these plant species and confirmes that medicinal plants are an important source of bioactive metabolites with anticancer or antileishmanial activities. Further studies to understand the molecular mechanisms governing their beneficial activity should be performed. (Less)
Abstract
In response to the challenges of their local environments, organisms produce of a large number of chemical diverse compounds with complex stereochemistry and reactive functional groups. These characteristics enable them to interact and bind specifically to biological target molecules and exert various biological activities, and have assured that Natural products continues to be an important source of bioactive compounds, which, for example, facilitate the search for new lead structures that can be developed into new pharmaceuticals.

This thesis describes the isolation by different chromatographic techniques, structure elucidation by NMR spectroscopy and high-resolution mass spectrometry and bioactivity of secondary metabolites of... (More)
In response to the challenges of their local environments, organisms produce of a large number of chemical diverse compounds with complex stereochemistry and reactive functional groups. These characteristics enable them to interact and bind specifically to biological target molecules and exert various biological activities, and have assured that Natural products continues to be an important source of bioactive compounds, which, for example, facilitate the search for new lead structures that can be developed into new pharmaceuticals.

This thesis describes the isolation by different chromatographic techniques, structure elucidation by NMR spectroscopy and high-resolution mass spectrometry and bioactivity of secondary metabolites of four medicinal plants.

Kaunia lasiophthalma G. was found to be particularly rich in sesquiterpene lactones and produced two new eudesmane derivatives (2.1 and 2.2) as well as a novel triterpene with a new carbon skeleton (2.3). The anticancer activity of several of the isolated metabolites was studied towards a panel of five breast-cancer cell lines, and compared with their cytotoxicity in normal-like breast epithelial MCF-10A cells. In addition, demonstrating the importance of the α-methylene-γ-lactone moiety present in most assayed compounds, a methyl cysteine adduct prepared from 2.10 was also evaluated. These compounds tested were found to exhibit different levels of anticancer and cytotoxicity.

The isolation and identification of the active constituents from extracts of Trixis antimenorrhoea and Lantana balansae possessing antileishmanial activity was carried out. Two new metabolites, the nortrixane 3.1 and the trixanolide 3.2, and eleven known compounds, terpenoids and flavonoids, were isolated from Trixis antimenorrhoea. Lantana balansae yielded eleven previously discovered metabolites, however, a potent cyclopentenone fatty acid derivative (3.16) and flavanones (3.17 and 3.18) are new classes of secondary metabolites for the genus Lantana. The structures of the compounds and the associated leishmanicidal activity towards L. amazonensis and L. braziliensis are discussed.

Three macrocyclic monoterpene O-glycosides (4.1-4.3) isolated from the leaves and small branches of Parkinsonia aculeate L. are reported. The structures were established using NMR and MS techniques. Particularly, 2D NMR experiments, HMQC, HMBC, COSY, TOCSY and ROESY, were crucial for the assembling of the structures. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Peña-Rodríguez, Luis Manuel, Centro de Investigación Científica de Yucatán (cicy) - México
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Terpenoid Sesquiterpene lactones Breast-cancer cell lines Cytotoxicity Antileishmanicial Structural characterization
pages
75 pages
publisher
Centre for Analysis and Synthesis, Department of Chemistry, Lund University
defense location
Lecture Hall B, at the Center of Chemistry and Chemical Engineering, Getingevägen 60, Lund University Faculty of Engineering, Lund
defense date
2014-10-01 09:30
ISBN
978-91-7422362-0
language
English
LU publication?
yes
id
d03cb57e-f629-4433-b692-cab829b40b39 (old id 4616699)
date added to LUP
2014-09-05 10:18:00
date last changed
2016-09-19 08:45:02
@phdthesis{d03cb57e-f629-4433-b692-cab829b40b39,
  abstract     = {In response to the challenges of their local environments, organisms produce of a large number of chemical diverse compounds with complex stereochemistry and reactive functional groups. These characteristics enable them to interact and bind specifically to biological target molecules and exert various biological activities, and have assured that Natural products continues to be an important source of bioactive compounds, which, for example, facilitate the search for new lead structures that can be developed into new pharmaceuticals.<br/><br>
This thesis describes the isolation by different chromatographic techniques, structure elucidation by NMR spectroscopy and high-resolution mass spectrometry and bioactivity of secondary metabolites of four medicinal plants.<br/><br>
Kaunia lasiophthalma G. was found to be particularly rich in sesquiterpene lactones and produced two new eudesmane derivatives (2.1 and 2.2) as well as a novel triterpene with a new carbon skeleton (2.3). The anticancer activity of several of the isolated metabolites was studied towards a panel of five breast-cancer cell lines, and compared with their cytotoxicity in normal-like breast epithelial MCF-10A cells. In addition, demonstrating the importance of the α-methylene-γ-lactone moiety present in most assayed compounds, a methyl cysteine adduct prepared from 2.10 was also evaluated. These compounds tested were found to exhibit different levels of anticancer and cytotoxicity. <br/><br>
The isolation and identification of the active constituents from extracts of Trixis antimenorrhoea and Lantana balansae possessing antileishmanial activity was carried out. Two new metabolites, the nortrixane 3.1 and the trixanolide 3.2, and eleven known compounds, terpenoids and flavonoids, were isolated from Trixis antimenorrhoea. Lantana balansae yielded eleven previously discovered metabolites, however, a potent cyclopentenone fatty acid derivative (3.16) and flavanones (3.17 and 3.18) are new classes of secondary metabolites for the genus Lantana. The structures of the compounds and the associated leishmanicidal activity towards L. amazonensis and L. braziliensis are discussed.<br/><br>
Three macrocyclic monoterpene O-glycosides (4.1-4.3) isolated from the leaves and small branches of Parkinsonia aculeate L. are reported. The structures were established using NMR and MS techniques. Particularly, 2D NMR experiments, HMQC, HMBC, COSY, TOCSY and ROESY, were crucial for the assembling of the structures.},
  author       = {Maldonado, Eliana},
  isbn         = {978-91-7422362-0},
  keyword      = {Terpenoid Sesquiterpene lactones Breast-cancer cell lines Cytotoxicity Antileishmanicial Structural characterization},
  language     = {eng},
  pages        = {75},
  publisher    = {Centre for Analysis and Synthesis, Department of Chemistry, Lund University},
  school       = {Lund University},
  title        = {Terpenoid Plant Metabolites - Structural Characterization and Biological Importance},
  year         = {2014},
}