{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-1386"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-1386","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"PREPARATION AND EVALUATION OF DECONSTRUCTION ANALOGS OF 7-DEOXYKALAFUNGIN AS AKT INHIBITORS","abstract":"Pyranonaphthoquinone lactones have been recently found to be selective inhibitors of the serine-threonine kinase AKT/PKB. AKT/PKB plays a major role in tumorigenesis, hence these compounds have a great potential to act as anti-cancer agents. They act by a novel bioreductive alkylation mechanism of inhibition of AKT/PKB. In this work, 7-deoxykalafungin, a pyranonaphthoquinone lactone and its deconstruction analogs were synthesized. The structural features of the compounds necessary to inhibit AKT1 potently and selectively were determined. It was observed that compounds with a pyran ring were more potent in inhibiting AKT1. Conversely, flexible compounds were found to be weak inhibitors of AKT1. Also, presence of a lactone ring was found to be favorable in inhibiting AKT1. Of the compounds tested, 7-deoxykalafungin was the most potent inhibitor of AKT1 (IC50 = 0.28 µM against AKT1) and compound 4-61 was the most potent inhibitor of PKA (IC50 = 0.43 µM against PKA).","abstract_html":"Pyranonaphthoquinone lactones have been recently found to be selective inhibitors of the serine-threonine kinase AKT/PKB. AKT/PKB plays a major role in tumorigenesis, hence these compounds have a great potential to act as anti-cancer agents. They act by a novel bioreductive alkylation mechanism of inhibition of AKT/PKB. In this work, 7-deoxykalafungin, a pyranonaphthoquinone lactone and its deconstruction analogs were synthesized. The structural features of the compounds necessary to inhibit AKT1 potently and selectively were determined. It was observed that compounds with a pyran ring were more potent in inhibiting AKT1. Conversely, flexible compounds were found to be weak inhibitors of AKT1. Also, presence of a lactone ring was found to be favorable in inhibiting AKT1. Of the compounds tested, 7-deoxykalafungin was the most potent inhibitor of AKT1 (IC50 = 0.28 µM against AKT1) and compound 4-61 was the most potent inhibitor of PKA (IC50 = 0.43 µM against PKA).","abstract_has_math":false,"creators":["Korwar, Sudha"],"institution":null,"degree_name":"Master of Science","degree_level":"Thesis","degree_discipline":"Pharmaceutical Sciences","degree_department":null,"school":null,"contributors":["Keith Ellis"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-07-27T07:00:00Z","date_published":"2012-07-27T07:00:00Z","updated_at":"2026-07-24T05:53:48Z","subjects":["7-Deoxykalafungin","AKT inhibitors","Heck coupling","Sharpless asymmetric dihydroxylation","Oxa-Pictet Spengler cyclization","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/387"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/387","href":"https://scholarscompass.vcu.edu/etd/387","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/9EME-4559","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Keith Ellis"]},{"key":"dc:creator","label":"Author","values":["Korwar, Sudha"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2017-08-09T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmaceutical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["7-Deoxykalafungin","AKT inhibitors","Heck coupling","Sharpless asymmetric dihydroxylation","Oxa-Pictet Spengler cyclization","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/9EME-4559","https://scholarscompass.vcu.edu/etd/387"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Pyranonaphthoquinone lactones have been recently found to be selective inhibitors of the serine-threonine kinase AKT/PKB. AKT/PKB plays a major role in tumorigenesis, hence these compounds have a great potential to act as anti-cancer agents. They act by a novel bioreductive alkylation mechanism of inhibition of AKT/PKB. In this work, 7-deoxykalafungin, a pyranonaphthoquinone lactone and its deconstruction analogs were synthesized. The structural features of the compounds necessary to inhibit AKT1 potently and selectively were determined. It was observed that compounds with a pyran ring were more potent in inhibiting AKT1. Conversely, flexible compounds were found to be weak inhibitors of AKT1. Also, presence of a lactone ring was found to be favorable in inhibiting AKT1. Of the compounds tested, 7-deoxykalafungin was the most potent inhibitor of AKT1 (IC50 = 0.28 µM against AKT1) and compound 4-61 was the most potent inhibitor of PKA (IC50 = 0.43 µM against PKA)."]},{"key":"dc:title","label":"Title","values":["PREPARATION AND EVALUATION OF DECONSTRUCTION ANALOGS OF 7-DEOXYKALAFUNGIN AS AKT INHIBITORS"]}]}],"canonical_facts":{"dc:contributor":["Keith Ellis"],"dc:creator":["Korwar, Sudha"],"dc:date.available":["2017-08-09T07:00:00Z"],"dc:description.abstract":["Pyranonaphthoquinone lactones have been recently found to be selective inhibitors of the serine-threonine kinase AKT/PKB. AKT/PKB plays a major role in tumorigenesis, hence these compounds have a great potential to act as anti-cancer agents. They act by a novel bioreductive alkylation mechanism of inhibition of AKT/PKB. In this work, 7-deoxykalafungin, a pyranonaphthoquinone lactone and its deconstruction analogs were synthesized. The structural features of the compounds necessary to inhibit AKT1 potently and selectively were determined. It was observed that compounds with a pyran ring were more potent in inhibiting AKT1. Conversely, flexible compounds were found to be weak inhibitors of AKT1. Also, presence of a lactone ring was found to be favorable in inhibiting AKT1. Of the compounds tested, 7-deoxykalafungin was the most potent inhibitor of AKT1 (IC50 = 0.28 µM against AKT1) and compound 4-61 was the most potent inhibitor of PKA (IC50 = 0.43 µM against PKA)."],"dc:identifier":["https://doi.org/10.25772/9EME-4559","https://scholarscompass.vcu.edu/etd/387"],"dc:rights":["© The Author"],"dc:subject":["7-Deoxykalafungin","AKT inhibitors","Heck coupling","Sharpless asymmetric dihydroxylation","Oxa-Pictet Spengler cyclization","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"],"dc:title":["PREPARATION AND EVALUATION OF DECONSTRUCTION ANALOGS OF 7-DEOXYKALAFUNGIN AS AKT INHIBITORS"],"thesis:degree_discipline":["Pharmaceutical Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T05:53:48Z"}