title: Natural product polyamines that inhibit human carbonic anhydrases.
abstract: Natural product compound collections have proven an effective way to access chemical diversity and recent findings have identified phenolic, coumarin, and polyamine natural products as atypical chemotypes that inhibit carbonic anhydrases (CAs). CA enzymes are implicated as targets of variable drug therapeutic classes and the discovery of selective, drug-like CA inhibitors is essential. Just two natural product polyamines, spermine and spermidine, have until now been investigated as CA inhibitors. In this study, five more complex natural product polyamines 1-5, derived from either marine sponge or fungi, were considered for inhibition of six different human CA isozymes of interest in therapeutic drug development. All compounds share a simple polyamine core fragment, either spermine or spermidine, yet display substantially different structure activity relationships for CA inhibition. Notably, polyamines 1-5 were submicromolar inhibitors of the cancer drug target CA IX, this is more potent than either spermine or spermidine.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
authors.affiliation: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Università degli Studi di Firenze, Via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Università degli Studi di Firenze, Via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.
authors.forename: Sally-Ann
authors.identifier: 0000-0003-4494-3687
authors.initials: SA
authors.lastname: Poulsen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001688:Biological Products / Q000008:administration & dosage* / Q000737:chemistry; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry; D006801:Humans; D013095:Spermidine / Q000008:administration & dosage* / Q000737:chemistry; D013096:Spermine / Q000008:administration & dosage* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; D013096:Spermine; C030123:coumarin; D002256:Carbonic Anhydrases; D013095:Spermidine