Phytochemical studies on Choisya x dewitteana 'Aztec Pearl'
Citation:ROPERO, DENISE RICOY, Phytochemical studies on Choisya x dewitteana 'Aztec Pearl', Trinity College Dublin.School of Pharmacy & Pharma. Sciences.PHARMACY AND PHARMACEUTICAL SCIENCES, 2018
Thesis - Denise Ropero.pdf (PDF) 8.647Mb
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Appendix II - Plos one.PDF (PDF) 1.903Mb
Appendix III - Brazilian Journal of Pharmacognosy.pdf (PDF) 596.7Kb
The thesis is introduced with a review of the genus Choisya. Here emphasis is placed on the botany, traditional uses, phytochemistry and ethnopharmacological studies. The main classes of compounds found in the genus are briefly described together with their associated pharmacological activities. The work described in this thesis centres the isolation of the major constituents of Choisya x dewitteana ‘Aztec Pearl’ and the evaluation of the antinociceptive activities of its extracts of the plant as well as on some of the isolated compounds. In addition, a HPTLC method was developed for the qualitative analysis of the flavonoids present in Choisya extracts while a HPLC method was developed and validated for both qualitative and quantitative analysis of the flavonoids and the major coumarin present in the genus Choisya. A new route to the synthesis of 4-arylcoumarin derivatives has been developed based on the structure of the major coumarin isolated in C. x dewitteana ‘Aztec Pearl’. The activity of these synthetic derivatives was evaluated in a tubulin polymerisation assay. Chapter two focus on the isolation of the major constituents of the leaves of C. x dewitteana ‘Aztec Pearl’. A novel furoquinoline alkaloid, (E)-4-((4,8-dimethoxyfuro[2,3-b]quinolin-7-yl)oxy)-2-methylbut-3-en-2-ol (2.09), three coumarins, puberulin (2.01), 6-methoxyl-7,8-methylenedioxycoumarin (2.02) and sabandinin (2.03); one sesquiterpene, 7-isopropyl-4-methyl-10-methylenecyclodec-5-ene-1,4-diol (2.04); eight alkaloids, 4-desmethoxychoisyine (2.05), anhydroevoxine (2.06), choisyine (2.07), evoxine (2.08), balfourolone (2.10), isobalfourodine (2.11) and balfourodinium methosalt (2.12) and one flavonoid, rutin (2.13) were isolated and characterised. These compounds have been isolated for the first time in this species. Solvent extracts of the leaves of C. x dewitteana ‘Aztec Pearl’ as well as anhydroevoxine and choisyine were evaluated for their antinociceptive activity and showed considerable activity. Chapter three centres on the development of chromatographic methods for the detection and quantification of flavonoids in extracts of C. x dewitteana ‘Aztec Pearl’ and C. ternata. HPTLC and HPLC-UV methods were developed and validated for the identification and quantification of four flavonoids glycosides, rutin, nicotiflorin, isoquercetin, astragalin and one coumarin in methanolic extracts of leaves, stem and flowers of C. x dewitteana ‘Aztec Pearl’ and C. ternata. Chapter four focuses on devising a suitable synthesis of 4-arylcoumarin derivatives based on the structure of the major coumarin isolated in C. x dewitteana ‘Aztec Pearl’. This synthetic pathway chosen to be tunable so that a diverse range of potential tubulin binding agents could be synthesised through this route. Particular emphasis was placed on designing a synthetic route that would allow for considerable flexibility in the type of substituents that could be placed on the A-ring of these 4-arylcoumarins. Following completion of the synthesis, test compounds were evaluated for their ability to inhibit tubulin polymerisation. All three compounds tested showed comparable activity to combretastatin A-4, a compound that is undergoing late stage clinical development for the treatment of different tumour types. All experimental information relating to the methods used for the isolation and synthesis of all compounds that were the subject of this thesis is outlined in Chapter 5.
Author: ROPERO, DENISE RICOY
Publisher:Trinity College Dublin. School of Pharmacy & Pharma. Sciences. Discipline of Pharmacy
Type of material:Thesis
Availability:Full text available