- Title
- Drugs from nature: 1. dynamin I inhibitors from Mexican marine algae; 2. chemical investigation of an Australian Aboriginal traditional remedy.
- Creator
- Zaleta-Pinet, Diana A.
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2014
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- The biological activity of 45 crude ethanolic extracts obtained from Mexican algae collected in the Baja California Peninsula were assessed. Extracts were tested for their antibacterial activity against the human pathogenic bacteria Staphylococcus epidermidis, Enterococcus faecalis and Moraxella catarrhalis and also for their inhibition towards dynamin I enzyme using a colourimetric assay. From the initial 45 extracts, 18 extracts were deemed suitable for further investigation because they showed significant activity in either one or both bioassays, representing a 40% hit rate. From the active extracts, 4 were selected for further fractionation. The ethanolic extract of the brown alga Dictyopteris delicatula was selected based on its antibacterial activity. Fractionation of the crude extract resulted in different active fractions which suffered loss of its activity in the last separation step. This activity loss suggested the presence of synergy within the compounds present in the fractions. A compound was isolated from an active fraction but due to its volatile nature it evaporated while 13C NMR data was being acquired and no structure elucidation was possible. Comparison of the 1H NMR obtained from the isolated compound with previous compounds isolated within the genus Dictyopteris suggested the prences of structures similar to the dictyopterenes. Fractionation of the crude extract obtained from brown alga Colpomenia tuberculata led to 3 fractions that presented inhibition against dynamin I. The 1H NMR spectrum of the fractions were similar but did not show any signs of a compound responsible for the activity. Further fractionation of this compound was impossible due to the rapid decomposition of the extract as well as the fractions. Chemical investigation of the crude extract of Laurencia pacifica was done based on its antibacterial activity as well as its activation of dynamin I. Fractionation of the extract resulted in the isolation of five pure compounds that were identified as isolaurenisol, isoaplysin, debromoisolaurinterol, debromoaplysinol, laur-11-en-10-ol and a 1:1 mixture of compounds 3α hydroxydebromoaplysin and 10-bromo-1,7-dien-3-ol, the latter one being reported for the first time. Antibacterially active compounds were found to be compounds isoaplysin, isolaurenisol, debromoisolaurinterol and debromoaplysionol, as previously reported; none of the isolated compounds presented dynamin I or dynamin II inhibition. Compounds were also tested against 11 cancer cell lines and 1 normal cell line. In this assay isoaplysin, isolaurenisol and debromoaplysionol presented higher activity and were selected for a second round of cancer biological testing where isoaplysin was shown to be the most active. Fractionation of the crude extract of Codium simulans that was selected for its inhibition towards dynaimin I led us to the isolation of a sterol, that was the main constituent of the crude extract. Based on the 1H and 13C data it was identified as clerosterol, which has been previously reported as the major sterol constituent of other Codium species. Clerosterol was found to be biologically inactive in inhibiting the enzymatic activity of dynamin I and dynamin II. In a second study, the medicinal potential of an Australian Aboriginal remedy, given to us by the Ngarrabul people, was evaluated. The traditional medicine is prepared as a tea with a native plant that was identified as Myoporum montanum. The acetone extract of the plant yielded six different furanosesquiterpenes: (+)myoporone, (–)-10,11-dehydromyoporone, (–) 10,11-dehydroisomyodesmone, (–)-10,11-dehydromyodesmone and the myoporum ketols as well as the constituent phytol. These furanosesquiterpenes have been previously isolated from Myoporum spp. and have been reported as being toxic. In addition to the furanosesquiterpenes, 14 carbocyclic sesquiterpenes were identified by GCMS as constituents of the acetone extract, which had antibacterial activity. Subsequently, the chemical investigation of the medicinal tea revealed the presence of three of the furanosesquiterpenes: myoporone, dehydromyoprone, and a new furanosesquiterpenes named 11 hydroxymyoporone. These compounds were assessed in the antibacterial assay, as well as a cytotoxic assay, where they showed high antibacterial activity but low cytotoxicity versus cancer cells.
- Subject
- natural products; secondary metabolites; Aboriginal medicine; algae metabolites
- Identifier
- http://hdl.handle.net/1959.13/1041664
- Identifier
- uon:13942
- Rights
- Copyright 2014 Diana A. Zaleta-Pinet
- Language
- eng
- Full Text
- Hits: 884
- Visitors: 1459
- Downloads: 382
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Abstract | 129 KB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Thesis | 7 MB | Adobe Acrobat PDF | View Details Download |