Kibdelones: novel anticancer polyketides from a rare Australian actinomycete.
The kibdelones are a novel family of bioactive heterocyclic polyketides produced by a rare soil actinomycete, Kibdelosporangium sp. (MST-108465). Complete relative stereostructures were assigned to kibdelones A-C (1-3), kibdelone B rhamnoside (5), 13-oxokibdelone A (7), and 25-methoxy-24-oxokibdelone C (8) on the basis of detailed spectroscopic analysis and chemical interconversion, as well as mechanistic and biosynthetic considerations. Under mild conditions, kibdelones B (2) and C (3) undergo a facile equilibration to kibdelones A-C (1-3), while kibdelone B rhamnoside (5) equilibrates to a mixture of kibdelone A-C rhamnosides (4-6). A plausible mechanism for this equilibration is proposed and involves air oxidation, quinone/hydroquinone redox transformations, and a choreographed sequence of keto/enol tautomerizations that aromatize ring C via a quinone methide intermediate. Kibdelones exhibit potent and selective cytotoxicity against a panel of human tumor cell lines and display significant antibacterial and nematocidal activity.
Ratnayake
Ranjala
R
Centre for Molecular Biodiversity, Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
Lacey
Ernest
E
Tennant
Shaun
S
Gill
Jennifer H
JH
Capon
Robert J
RJ
D039903:Actinobacteria / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000969:Antinematodal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001711:Biotransformation; D045744:Cell Line, Tumor / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry; D045563:Indolequinones / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry; D012210:Rhamnose / Q000031:analogs & derivatives; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D000969:Antinematodal Agents; D006571:Heterocyclic Compounds; D006873:Hydroquinones; D045563:Indolequinones; D018942:Macrolides; D011809:Quinones; C068040:quinone methide; D012210:Rhamnose; C031927:hydroquinone