{"id":{"repo_id":"auckland-ms","oai_identifier":"oai:researchspace.auckland.ac.nz:2292/22763"},"canonical_url":"https://search.dev.ndltd.org/etd/auckland-ms/oai:researchspace.auckland.ac.nz:2292/22763","repository":{"repo_id":"auckland-ms","name":"University of Auckland","base_url":"https://researchspace.auckland.ac.nz/server/oai/request"},"display":{"title":"A Drug Discovery Study: Inhibitor Design for HRV 3C Protease Based on the Scaffold of (-)-Thysanone","abstract":"This thesis is concerned with the drug development study against the common cold based on the ( )-thysanone scaffold. The common cold, majorly caused by the Human Rhinovirus, still remains one of the major causes of work-loss in industrialised countries and currently only symptomatic treatment is available to treat these viral infections. Thus, even though this illness is not life threatening, a direct anti-viral drug would be of significant benefit. ( )-Thysanone was isolated from the fungus Thysanophora penicilloides and was shown to inhibit the viral enzyme HRV 3C protease with an IC50 of 13 μg/mL (47 μM). HRV 3C protease is required for viral replication, thus inhibition of this enzyme will also inhibit the reproduction of the virus. O O O OH OH HO 7 9 (−)-thysanone This study is divided into three parts. The first part gives a brief introduction to the common cold, its major cause -the Human Rhinovirus- and attempts for drug development. The second part describes the determination of structure activity relationships (SAR) of a first generation library of inhibitors based on the ( )-thysanone scaffold and also pharmacodynamic aspects, such as the molecular mechanism of action of ( )-thysanone with HRV 3C protease, cross interactions with other important human proteases and cytotoxicity assays of our library of compounds against a human lung epithelia cell line. The third part then describes the syntheses of all analogues. Two literature known preparations of the natural product and the 7,9-dideoxy analogue were followed as well as the development of a new strategy for the synthesis of 2-carbathysanone using a Hauser-Kraus annulation as key-step and the development of a new synthetic approach for 7-deoxy analogues using an oxa-Pictet-Spengler reaction in the key step. This oxa-Pictet-Spengler approach was also used for development of a new synthetic strategy for thysanone also involving C-H activation chemistry.","abstract_html":"This thesis is concerned with the drug development study against the common cold based on the ( )-thysanone scaffold. The common cold, majorly caused by the Human Rhinovirus, still remains one of the major causes of work-loss in industrialised countries and currently only symptomatic treatment is available to treat these viral infections. Thus, even though this illness is not life threatening, a direct anti-viral drug would be of significant benefit. ( )-Thysanone was isolated from the fungus Thysanophora penicilloides and was shown to inhibit the viral enzyme HRV 3C protease with an IC50 of 13 μg/mL (47 μM). HRV 3C protease is required for viral replication, thus inhibition of this enzyme will also inhibit the reproduction of the virus. O O O OH OH HO 7 9 (−)-thysanone This study is divided into three parts. The first part gives a brief introduction to the common cold, its major cause -the Human Rhinovirus- and attempts for drug development. The second part describes the determination of structure activity relationships (SAR) of a first generation library of inhibitors based on the ( )-thysanone scaffold and also pharmacodynamic aspects, such as the molecular mechanism of action of ( )-thysanone with HRV 3C protease, cross interactions with other important human proteases and cytotoxicity assays of our library of compounds against a human lung epithelia cell line. The third part then describes the syntheses of all analogues. Two literature known preparations of the natural product and the 7,9-dideoxy analogue were followed as well as the development of a new strategy for the synthesis of 2-carbathysanone using a Hauser-Kraus annulation as key-step and the development of a new synthetic approach for 7-deoxy analogues using an oxa-Pictet-Spengler reaction in the key step. This oxa-Pictet-Spengler approach was also used for development of a new synthetic strategy for thysanone also involving C-H activation chemistry.","abstract_has_math":false,"creators":["Schünemann, Katrin"],"institution":"ResearchSpace@Auckland","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Brimble, M","Fraser, J"],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014","date_published":"2014","updated_at":"2026-07-24T01:02:59Z","subjects":[],"languages":[],"rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. 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( )-Thysanone was isolated from the fungus Thysanophora penicilloides and was shown to inhibit the viral enzyme HRV 3C protease with an IC50 of 13 μg/mL (47 μM). HRV 3C protease is required for viral replication, thus inhibition of this enzyme will also inhibit the reproduction of the virus. O O O OH OH HO 7 9 (−)-thysanone This study is divided into three parts. The first part gives a brief introduction to the common cold, its major cause -the Human Rhinovirus- and attempts for drug development. The second part describes the determination of structure activity relationships (SAR) of a first generation library of inhibitors based on the ( )-thysanone scaffold and also pharmacodynamic aspects, such as the molecular mechanism of action of ( )-thysanone with HRV 3C protease, cross interactions with other important human proteases and cytotoxicity assays of our library of compounds against a human lung epithelia cell line. The third part then describes the syntheses of all analogues. Two literature known preparations of the natural product and the 7,9-dideoxy analogue were followed as well as the development of a new strategy for the synthesis of 2-carbathysanone using a Hauser-Kraus annulation as key-step and the development of a new synthetic approach for 7-deoxy analogues using an oxa-Pictet-Spengler reaction in the key step. This oxa-Pictet-Spengler approach was also used for development of a new synthetic strategy for thysanone also involving C-H activation chemistry."]},{"key":"dc:title","label":"Title","values":["A Drug Discovery Study: Inhibitor Design for HRV 3C Protease Based on the Scaffold of (-)-Thysanone"]}]}],"canonical_facts":{"dc:contributor.advisor":["Brimble, M","Fraser, J"],"dc:creator":["Schünemann, Katrin"],"dc:date.accessioned":["2014-08-18T22:27:28Z"],"dc:date.issued":["2014"],"dc:description.abstract":["This thesis is concerned with the drug development study against the common cold based on the ( )-thysanone scaffold. The common cold, majorly caused by the Human Rhinovirus, still remains one of the major causes of work-loss in industrialised countries and currently only symptomatic treatment is available to treat these viral infections. Thus, even though this illness is not life threatening, a direct anti-viral drug would be of significant benefit. ( )-Thysanone was isolated from the fungus Thysanophora penicilloides and was shown to inhibit the viral enzyme HRV 3C protease with an IC50 of 13 μg/mL (47 μM). HRV 3C protease is required for viral replication, thus inhibition of this enzyme will also inhibit the reproduction of the virus. O O O OH OH HO 7 9 (−)-thysanone This study is divided into three parts. The first part gives a brief introduction to the common cold, its major cause -the Human Rhinovirus- and attempts for drug development. The second part describes the determination of structure activity relationships (SAR) of a first generation library of inhibitors based on the ( )-thysanone scaffold and also pharmacodynamic aspects, such as the molecular mechanism of action of ( )-thysanone with HRV 3C protease, cross interactions with other important human proteases and cytotoxicity assays of our library of compounds against a human lung epithelia cell line. The third part then describes the syntheses of all analogues. Two literature known preparations of the natural product and the 7,9-dideoxy analogue were followed as well as the development of a new strategy for the synthesis of 2-carbathysanone using a Hauser-Kraus annulation as key-step and the development of a new synthetic approach for 7-deoxy analogues using an oxa-Pictet-Spengler reaction in the key step. This oxa-Pictet-Spengler approach was also used for development of a new synthetic strategy for thysanone also involving C-H activation chemistry."],"dc:identifier.uri":["https://hdl.handle.net/2292/22763"],"dc:publisher":["ResearchSpace@Auckland"],"dc:rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher."],"dc:rights.uri":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"],"dc:title":["A Drug Discovery Study: Inhibitor Design for HRV 3C Protease Based on the Scaffold of (-)-Thysanone"],"dc:type":["Thesis"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Auckland"]},"updated_at":"2026-07-24T01:02:59Z"}