{"id":{"repo_id":"u-iceland","oai_identifier":"oai:skemman.is:1946/37756"},"canonical_url":"https://search.dev.ndltd.org/etd/u-iceland/oai:skemman.is:1946/37756","repository":{"repo_id":"u-iceland","name":"University of Iceland","base_url":"https://skemman.is/oai/request"},"display":{"title":"Exploring 1,3-dihydroxyphenazine 5,10-dioxide as a new antimicrobial lead. Synthesis and in vitro evaluations","abstract":"The development of multi-drug resistant (MDR) pathogens is a rapidly growing problem throughout the years which continues to threaten millions of lives and the global healthcare. Supply and development of new antibiotics has diminished and limited treatment options are left to manage infections caused by MDR pathogens. As recent events have shown, drug development against infectious pathogens is especially important to counteract this problem and screening for new drug leads is necessary. Iodinin and its O-methylated derivative; myxin are natural products belonging to the compound class of phenazine 5,10-dioxides which have been shown to possess potent antitumor and broad-spectrum antimicrobial activities in vitro. Some of their synthetic derivatives have also been shown to possess potent antimicrobial activities, such as 1,3-dihydroxyphenazine 5,10-dioxide, rendering them as valuable drug leads for potential chemotherapeutic agents. The aim of this study was to synthesize analogs from the lead compound 1,3-dihydroxyphenazine 5,10-dioxide and explore their antimicrobial activities in vitro. The synthesis was achieved by exposing 1,3-dihydroxyphenazine 5,10-dioxide to either commercially available carbamoyl chlorides or alkyl halides. Another aim of this study was to explore synthetic routes towards formyl substituted phenazine 5,10-dioxides. The chemical structure, mass and purity of all successfully synthesized analogs was confirmed with 1H-NMR, 13C-NMR, HRMS and HPLC analysis. Antimicrobial activities of eight characterized 1,3-O-functionalized phenazine 5,10-dioxides were evaluated in vitro against both S. aureus and E. coli and compared to the lead scaffold 1,3-dihydroxyphenazine 5,10-dioxide as well as the natural products iodinin and myxin. 1,3-Bis-substituted analogs showed potent activity against S. aureus with similar potency as myxin. 1-Hydroxy-3-methoxyphenazine 5,10-dioxide was further confirmed to be a highly potent compound and so did its close derivative, 3-ethoxy-1-hydroxyphenazine 5,10-dioxide, with both compounds containing an exploitable phenol moiety for further functionalization and drug development.","abstract_html":"The development of multi-drug resistant (MDR) pathogens is a rapidly growing problem throughout the years which continues to threaten millions of lives and the global healthcare. Supply and development of new antibiotics has diminished and limited treatment options are left to manage infections caused by MDR pathogens. As recent events have shown, drug development against infectious pathogens is especially important to counteract this problem and screening for new drug leads is necessary. Iodinin and its O-methylated derivative; myxin are natural products belonging to the compound class of phenazine 5,10-dioxides which have been shown to possess potent antitumor and broad-spectrum antimicrobial activities in vitro. Some of their synthetic derivatives have also been shown to possess potent antimicrobial activities, such as 1,3-dihydroxyphenazine 5,10-dioxide, rendering them as valuable drug leads for potential chemotherapeutic agents. The aim of this study was to synthesize analogs from the lead compound 1,3-dihydroxyphenazine 5,10-dioxide and explore their antimicrobial activities in vitro. The synthesis was achieved by exposing 1,3-dihydroxyphenazine 5,10-dioxide to either commercially available carbamoyl chlorides or alkyl halides. Another aim of this study was to explore synthetic routes towards formyl substituted phenazine 5,10-dioxides. The chemical structure, mass and purity of all successfully synthesized analogs was confirmed with 1H-NMR, 13C-NMR, HRMS and HPLC analysis. Antimicrobial activities of eight characterized 1,3-O-functionalized phenazine 5,10-dioxides were evaluated in vitro against both S. aureus and E. coli and compared to the lead scaffold 1,3-dihydroxyphenazine 5,10-dioxide as well as the natural products iodinin and myxin. 1,3-Bis-substituted analogs showed potent activity against S. aureus with similar potency as myxin. 1-Hydroxy-3-methoxyphenazine 5,10-dioxide was further confirmed to be a highly potent compound and so did its close derivative, 3-ethoxy-1-hydroxyphenazine 5,10-dioxide, with both compounds containing an exploitable phenol moiety for further functionalization and drug development.","abstract_has_math":false,"creators":["Ísak Máni Stefánsson 1997-"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Háskóli Íslands"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-04-19T11:18:05Z","date_published":"2021-04-19T11:18:05Z","updated_at":"2026-07-27T21:36:33Z","subjects":["Lyfjafræði"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1946/37756","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Háskóli Íslands"]},{"key":"dc:creator","label":"Author","values":["Ísak Máni Stefánsson 1997-"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-04-19T11:18:04Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-04-19T11:18:04Z"]},{"key":"dc:date.issued","label":"Date","values":["2021-04-19T11:18:05Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Lyfjafræði"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1946/37756"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The development of multi-drug resistant (MDR) pathogens is a rapidly growing problem throughout the years which continues to threaten millions of lives and the global healthcare. Supply and development of new antibiotics has diminished and limited treatment options are left to manage infections caused by MDR pathogens. As recent events have shown, drug development against infectious pathogens is especially important to counteract this problem and screening for new drug leads is necessary. Iodinin and its O-methylated derivative; myxin are natural products belonging to the compound class of phenazine 5,10-dioxides which have been shown to possess potent antitumor and broad-spectrum antimicrobial activities in vitro. Some of their synthetic derivatives have also been shown to possess potent antimicrobial activities, such as 1,3-dihydroxyphenazine 5,10-dioxide, rendering them as valuable drug leads for potential chemotherapeutic agents. The aim of this study was to synthesize analogs from the lead compound 1,3-dihydroxyphenazine 5,10-dioxide and explore their antimicrobial activities in vitro. The synthesis was achieved by exposing 1,3-dihydroxyphenazine 5,10-dioxide to either commercially available carbamoyl chlorides or alkyl halides. Another aim of this study was to explore synthetic routes towards formyl substituted phenazine 5,10-dioxides. The chemical structure, mass and purity of all successfully synthesized analogs was confirmed with 1H-NMR, 13C-NMR, HRMS and HPLC analysis. Antimicrobial activities of eight characterized 1,3-O-functionalized phenazine 5,10-dioxides were evaluated in vitro against both S. aureus and E. coli and compared to the lead scaffold 1,3-dihydroxyphenazine 5,10-dioxide as well as the natural products iodinin and myxin. 1,3-Bis-substituted analogs showed potent activity against S. aureus with similar potency as myxin. 1-Hydroxy-3-methoxyphenazine 5,10-dioxide was further confirmed to be a highly potent compound and so did its close derivative, 3-ethoxy-1-hydroxyphenazine 5,10-dioxide, with both compounds containing an exploitable phenol moiety for further functionalization and drug development.","Sýkingar of völdum fjölónæmra (e. MDR) baktería er alvarlegt heilsufarsvandamál sem hefur farið ört vaxandi í gegnum árin. Á sama tíma hefur framboð og þróun á nýjum sýklalyfjum farið minnkandi og nothæf meðferðarúrræði gegn þessum sýkingum farið fækkandi. Núverandi aðstæður hafa varpað ljósi á mikilvægi lyfjaþróunar gegn smitandi örverum til að sporna við þessu vandamáli. Náttúruefnin iodinín og mónómetýleruð afleiða þess; myxín eru efnasambönd í flokki fenazín 5,10-díoxíða sem hafa sýnt fram á mikla æxlis- og bakteríuhemjandi eiginleika in vitro. Sumar efnasmíðaðar afleiður náttúruefnanna hafa einnig sýnt fram á eftirsóknarverða bakteríuhemjandi eiginleika og þar má til dæmis nefna 1,3-díhýdroxýfenazín 5,10-díoxíð sem gerir þessar sameindir að áhugaverðum lyfjasprotum til frekari lyfjaþróunar. Markmið rannsóknarinnar var að efnasmíða nýjar afleiður af sýklalyfjasprotanum 1,3-díhýdroxýfenazín 5,10-díoxíð með því að hvarfa það við annaðhvort karbamóýl klóríð eða alkýl halíð og meta bakteríuhemjandi eiginleika þeirra in vitro. Annað markmið rannsóknarinnar var að þróa efnasmíðaaðferðir fyrir formýl setin fenazín 5,10-díoxíð. Efnabygging, massi og hreinleiki smíðaðra efna voru staðfest með kjarnsegulómun (1H-NMR og 13C-NMR), massagreiningu (HRMS) og vökvagreiningu (HPLC). Bakteríuhemjandi eiginleikar átta nýsmíðaðra 1,3-setinna fenazín 5,10-díoxíða voru rannsakaðir og bornir saman við lyfjasprotann 1,3-díhýdroxýfenazín 5,10-díoxíð og náttúruefnin iodinín og myxín gegn S. aureus og E. coli. 1,3-Tvísetin-fenazín 5,10-díoxíð sýndu fram á eftirsóknaverða bakteríuhemjandi virkni gegn S. aureus með svipaða virkni og myxín. 1-Hýdroxý-3-metoxýfenazín 5,10-díoxíð sýndi enn fremur búa yfir mikilvirkum bakteríuhemjandi eiginleikum og sömuleiðis nálæg afleiða þess, 3-etoxý-1-hýdroxýfenazín 5,10-díoxíð. Báðar sameindirnar innihalda virkjanlegt fenól í stöðu 1 sem býður upp á möguleikann á frekari afleiðumyndun og áframhaldandi lyfjaþróun."]},{"key":"dc:title","label":"Title","values":["Exploring 1,3-dihydroxyphenazine 5,10-dioxide as a new antimicrobial lead. Synthesis and in vitro evaluations"]}]}],"canonical_facts":{"dc:contributor":["Háskóli Íslands"],"dc:creator":["Ísak Máni Stefánsson 1997-"],"dc:date.accessioned":["2021-04-19T11:18:04Z"],"dc:date.available":["2021-04-19T11:18:04Z"],"dc:date.issued":["2021-04-19T11:18:05Z"],"dc:description.abstract":["The development of multi-drug resistant (MDR) pathogens is a rapidly growing problem throughout the years which continues to threaten millions of lives and the global healthcare. Supply and development of new antibiotics has diminished and limited treatment options are left to manage infections caused by MDR pathogens. As recent events have shown, drug development against infectious pathogens is especially important to counteract this problem and screening for new drug leads is necessary. Iodinin and its O-methylated derivative; myxin are natural products belonging to the compound class of phenazine 5,10-dioxides which have been shown to possess potent antitumor and broad-spectrum antimicrobial activities in vitro. Some of their synthetic derivatives have also been shown to possess potent antimicrobial activities, such as 1,3-dihydroxyphenazine 5,10-dioxide, rendering them as valuable drug leads for potential chemotherapeutic agents. The aim of this study was to synthesize analogs from the lead compound 1,3-dihydroxyphenazine 5,10-dioxide and explore their antimicrobial activities in vitro. The synthesis was achieved by exposing 1,3-dihydroxyphenazine 5,10-dioxide to either commercially available carbamoyl chlorides or alkyl halides. Another aim of this study was to explore synthetic routes towards formyl substituted phenazine 5,10-dioxides. The chemical structure, mass and purity of all successfully synthesized analogs was confirmed with 1H-NMR, 13C-NMR, HRMS and HPLC analysis. Antimicrobial activities of eight characterized 1,3-O-functionalized phenazine 5,10-dioxides were evaluated in vitro against both S. aureus and E. coli and compared to the lead scaffold 1,3-dihydroxyphenazine 5,10-dioxide as well as the natural products iodinin and myxin. 1,3-Bis-substituted analogs showed potent activity against S. aureus with similar potency as myxin. 1-Hydroxy-3-methoxyphenazine 5,10-dioxide was further confirmed to be a highly potent compound and so did its close derivative, 3-ethoxy-1-hydroxyphenazine 5,10-dioxide, with both compounds containing an exploitable phenol moiety for further functionalization and drug development.","Sýkingar of völdum fjölónæmra (e. MDR) baktería er alvarlegt heilsufarsvandamál sem hefur farið ört vaxandi í gegnum árin. Á sama tíma hefur framboð og þróun á nýjum sýklalyfjum farið minnkandi og nothæf meðferðarúrræði gegn þessum sýkingum farið fækkandi. Núverandi aðstæður hafa varpað ljósi á mikilvægi lyfjaþróunar gegn smitandi örverum til að sporna við þessu vandamáli. Náttúruefnin iodinín og mónómetýleruð afleiða þess; myxín eru efnasambönd í flokki fenazín 5,10-díoxíða sem hafa sýnt fram á mikla æxlis- og bakteríuhemjandi eiginleika in vitro. Sumar efnasmíðaðar afleiður náttúruefnanna hafa einnig sýnt fram á eftirsóknarverða bakteríuhemjandi eiginleika og þar má til dæmis nefna 1,3-díhýdroxýfenazín 5,10-díoxíð sem gerir þessar sameindir að áhugaverðum lyfjasprotum til frekari lyfjaþróunar. Markmið rannsóknarinnar var að efnasmíða nýjar afleiður af sýklalyfjasprotanum 1,3-díhýdroxýfenazín 5,10-díoxíð með því að hvarfa það við annaðhvort karbamóýl klóríð eða alkýl halíð og meta bakteríuhemjandi eiginleika þeirra in vitro. Annað markmið rannsóknarinnar var að þróa efnasmíðaaðferðir fyrir formýl setin fenazín 5,10-díoxíð. Efnabygging, massi og hreinleiki smíðaðra efna voru staðfest með kjarnsegulómun (1H-NMR og 13C-NMR), massagreiningu (HRMS) og vökvagreiningu (HPLC). Bakteríuhemjandi eiginleikar átta nýsmíðaðra 1,3-setinna fenazín 5,10-díoxíða voru rannsakaðir og bornir saman við lyfjasprotann 1,3-díhýdroxýfenazín 5,10-díoxíð og náttúruefnin iodinín og myxín gegn S. aureus og E. coli. 1,3-Tvísetin-fenazín 5,10-díoxíð sýndu fram á eftirsóknaverða bakteríuhemjandi virkni gegn S. aureus með svipaða virkni og myxín. 1-Hýdroxý-3-metoxýfenazín 5,10-díoxíð sýndi enn fremur búa yfir mikilvirkum bakteríuhemjandi eiginleikum og sömuleiðis nálæg afleiða þess, 3-etoxý-1-hýdroxýfenazín 5,10-díoxíð. Báðar sameindirnar innihalda virkjanlegt fenól í stöðu 1 sem býður upp á möguleikann á frekari afleiðumyndun og áframhaldandi lyfjaþróun."],"dc:identifier.uri":["http://hdl.handle.net/1946/37756"],"dc:language.iso":["en"],"dc:subject":["Lyfjafræði"],"dc:title":["Exploring 1,3-dihydroxyphenazine 5,10-dioxide as a new antimicrobial lead. Synthesis and in vitro evaluations"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:36:33Z"}