Biologically Interesting Compounds from Natural Sources.

Veronica de la Parra

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Natural products have traditionally played a major role in the drug discovery process. Besides constituting extremely popular drugs in the market, and an ever-increasing source of interesting and novel chemical structures, they have also aided the characterization of many a pharmacological target. And although natural product-oriented research has suffered from a declining interest from the pharmaceutical companies, this thesis shows how compounds isolated from different natural sources can still constitute interesting leads for future drug development, while aiding a better understanding of the nature of the interaction between different pharmacological targets and their agonists.

To this effect, this thesis first describes the isolation and structural elucidation of four new terpenoid compounds from fermentation broths produced by an Ascomycete fungus. Two of these compounds exhibit potent cytotoxic properties, related to their ability to affect protein, RNA and DNA synthesis.

Further on, the pharmacological characterization of the vasorelaxing activity of allyl mercaptan, the major metabolite of garlic, as well as of some of its chemical derivatives is described. The active compounds are able to excite primary sensory neurons and appear to activate members of the transient receptor potential channel family TRPA1. The results highlight the importance of both an allyl moiety and a thiol group in order to retain the activity.

Finally, the isolation and structural elucidation of three new sesquiterpenes and a new pyridinium alkaloid from an extract of Cacalia decomposita, a Mexican plant traditionally used against diabetes, is described. Of these, 13-hydroxy-14-angeloyloxy-1,2-dehydrocacalol is a strong agonist of a GPR40, a G-protein coupled receptor, which appears to have an important role in the development of diabetes mellitus type II.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Centre for Analysis and Synthesis
Supervisors/Advisors
  • Sterner, Olov, Supervisor
Award date2006 Nov 24
Publisher
Print ISBNs978-91-628-6996-0
Publication statusPublished - 2006

Bibliographical note

Defence details

Date: 2006-11-24
Time: 13:30
Place: Kemicentrum, Sal B

External reviewer(s)

Name: Borg-Karlson, Anna-Karin
Title: Prof.
Affiliation: Organisk Kemi, Kungliga Tekniska Högskolan, Stockholm

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The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)

Subject classification (UKÄ)

  • Organic Chemistry

Keywords

  • cytotoxicity
  • Natural products
  • terpenoids
  • vasorelaxant activity
  • allylmercaptane
  • diabetes mellitus type II
  • Organisk kemi
  • Organic chemistry
  • Cacalia decomposita
  • GPR40 receptor
  • TRP channel

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