{"id":{"repo_id":"mississippi","oai_identifier":"oai:egrove.olemiss.edu:etd-2342"},"canonical_url":"https://search.dev.ndltd.org/etd/mississippi/oai:egrove.olemiss.edu:etd-2342","repository":{"repo_id":"mississippi","name":"University of Mississippi","base_url":"https://egrove.olemiss.edu/do/oai/"},"display":{"title":"Potential Natural Product Phosphodiesterase Inhibitors","abstract":"Three different studies set forth to investigate the role of phosphodiesterase (PDE) enzyme inhibitors in sexual dysfunction and mood regulation. First, naturalproducts were screened by computer modeling of PDE5A1. Second, compounds were isolated from a plant traditionally used as an aphrodisiac. Third, a new synthesis of psychoactive PDE4 inhibitor was attempted. An in silico screen was performed using chemical structures of isolated compounds thought to have some PDE inhibitory activity based on traditional use of the plants. A collection of compounds with structures similar to known natural product inhibitors was also included in the docking library. Glide docking software (Schrödinger) was used to score compounds based on their modeled interactions with the PDE5A1 enzyme. The compounds that shothe best scores were assayed for in vitro PDE inhibitory activity. Enzymatic screening suggested some inhibition of PDE5A1 by selected compounds. Four of seven compounds shogreater than 70% inhibition at 100 &mgr;M concentration. Tongkat ali (Eurycoma longifolia Jack) root material was subjected to chromatographic separations in an attempt to discover new PDE inhibitors. Only known terpenes, sterols and alkaloids were identified. However, one new x-ray crystal structure of a sterol previously unreported in E. lonigfolia was determined. Mesembrine, a known alkaloidal PDE inhibitor, has been a subject of many synthetic studies. A synthetic route was initiated using a diastereoselective Michael addition reaction to generate the target quaternary center.","abstract_html":"Three different studies set forth to investigate the role of phosphodiesterase (PDE) enzyme inhibitors in sexual dysfunction and mood regulation. First, naturalproducts were screened by computer modeling of PDE5A1. Second, compounds were isolated from a plant traditionally used as an aphrodisiac. Third, a new synthesis of psychoactive PDE4 inhibitor was attempted. An in silico screen was performed using chemical structures of isolated compounds thought to have some PDE inhibitory activity based on traditional use of the plants. A collection of compounds with structures similar to known natural product inhibitors was also included in the docking library. Glide docking software (Schrödinger) was used to score compounds based on their modeled interactions with the PDE5A1 enzyme. The compounds that shothe best scores were assayed for in vitro PDE inhibitory activity. Enzymatic screening suggested some inhibition of PDE5A1 by selected compounds. Four of seven compounds shogreater than 70% inhibition at 100 &mgr;M concentration. Tongkat ali (Eurycoma longifolia Jack) root material was subjected to chromatographic separations in an attempt to discover new PDE inhibitors. Only known terpenes, sterols and alkaloids were identified. However, one new x-ray crystal structure of a sterol previously unreported in E. lonigfolia was determined. Mesembrine, a known alkaloidal PDE inhibitor, has been a subject of many synthetic studies. A synthetic route was initiated using a diastereoselective Michael addition reaction to generate the target quaternary center.","abstract_has_math":false,"creators":["Cunningham, Michael John"],"institution":null,"degree_name":"M.S. in Pharmaceutical Science","degree_level":"Thesis","degree_discipline":"Pharmaceutics and Drug Delivery","degree_department":null,"school":null,"contributors":["Ikhlas A. Khan","Jordan K. Zjawiony","Daneel Ferreira"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-01-01T08:00:00Z","date_published":"2013-01-01T08:00:00Z","updated_at":"2026-07-24T03:06:44Z","subjects":["crinosterol","mesembrine","PDE4","PDE5","phosphodiesterase","tongkat","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://egrove.olemiss.edu/etd/1343","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Ikhlas A. Khan","Jordan K. 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First, naturalproducts were screened by computer modeling of PDE5A1. Second, compounds were isolated from a plant traditionally used as an aphrodisiac. Third, a new synthesis of psychoactive PDE4 inhibitor was attempted. An in silico screen was performed using chemical structures of isolated compounds thought to have some PDE inhibitory activity based on traditional use of the plants. A collection of compounds with structures similar to known natural product inhibitors was also included in the docking library. Glide docking software (Schrödinger) was used to score compounds based on their modeled interactions with the PDE5A1 enzyme. The compounds that shothe best scores were assayed for in vitro PDE inhibitory activity. Enzymatic screening suggested some inhibition of PDE5A1 by selected compounds. Four of seven compounds shogreater than 70% inhibition at 100 &mgr;M concentration. Tongkat ali (Eurycoma longifolia Jack) root material was subjected to chromatographic separations in an attempt to discover new PDE inhibitors. Only known terpenes, sterols and alkaloids were identified. However, one new x-ray crystal structure of a sterol previously unreported in E. lonigfolia was determined. Mesembrine, a known alkaloidal PDE inhibitor, has been a subject of many synthetic studies. A synthetic route was initiated using a diastereoselective Michael addition reaction to generate the target quaternary center."]},{"key":"dc:title","label":"Title","values":["Potential Natural Product Phosphodiesterase Inhibitors"]}]}],"canonical_facts":{"dc:contributor":["Ikhlas A. Khan","Jordan K. Zjawiony","Daneel Ferreira"],"dc:creator":["Cunningham, Michael John"],"dc:date.available":["2020-07-21T07:00:00Z"],"dc:description.abstract":["Three different studies set forth to investigate the role of phosphodiesterase (PDE) enzyme inhibitors in sexual dysfunction and mood regulation. First, naturalproducts were screened by computer modeling of PDE5A1. Second, compounds were isolated from a plant traditionally used as an aphrodisiac. Third, a new synthesis of psychoactive PDE4 inhibitor was attempted. An in silico screen was performed using chemical structures of isolated compounds thought to have some PDE inhibitory activity based on traditional use of the plants. A collection of compounds with structures similar to known natural product inhibitors was also included in the docking library. Glide docking software (Schrödinger) was used to score compounds based on their modeled interactions with the PDE5A1 enzyme. The compounds that shothe best scores were assayed for in vitro PDE inhibitory activity. Enzymatic screening suggested some inhibition of PDE5A1 by selected compounds. Four of seven compounds shogreater than 70% inhibition at 100 &mgr;M concentration. Tongkat ali (Eurycoma longifolia Jack) root material was subjected to chromatographic separations in an attempt to discover new PDE inhibitors. Only known terpenes, sterols and alkaloids were identified. However, one new x-ray crystal structure of a sterol previously unreported in E. lonigfolia was determined. Mesembrine, a known alkaloidal PDE inhibitor, has been a subject of many synthetic studies. A synthetic route was initiated using a diastereoselective Michael addition reaction to generate the target quaternary center."],"dc:identifier":["https://egrove.olemiss.edu/etd/1343"],"dc:subject":["crinosterol","mesembrine","PDE4","PDE5","phosphodiesterase","tongkat","Pharmacy and Pharmaceutical Sciences"],"dc:title":["Potential Natural Product Phosphodiesterase Inhibitors"],"thesis:degree_discipline":["Pharmaceutics and Drug Delivery"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S. in Pharmaceutical Science"]},"updated_at":"2026-07-24T03:06:44Z"}