Antipodal crambescin A2 homologues from the marine sponge Pseudaxinella reticulata. Antifungal structure-activity relationships.
Investigation of antifungal natural products from the marine sponge Pseudaxinella reticulata from the Bahamas led to the discovery of new crambescin homologues (1, 2) and enantiomers (3, 4) of known natural products. The cyclic-guanidine structures were solved through analysis of 2D NMR, MS-MS, and CD data. The absolute configurations of 1-4 were established as 13R-opposite of known homologues reported from Crambe crambe obtained from the Mediterranean Sea-by comparison of their CD spectra with predicted Cotton effects obtained from DFT calculations. Antifungal activities of 1-4 against the pathogenic strains Candida albicans and Cryptococcus sp. were observed to correlate potency (MIC50 and MIC90) with the length of the alkyl side chain.
†Department of Chemistry and Biochemistry and §Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive MC-0358, La Jolla, California 92093-0358, United States.
Matthew T
MT
Jamison
†Department of Chemistry and Biochemistry and §Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive MC-0358, La Jolla, California 92093-0358, United States.
Tadeusz F
TF
Molinski
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001444:Bahamas; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D003454:Cryptococcus / Q000187:drug effects; D006146:Guanidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008386:Marine Biology; D008522:Mediterranean Sea; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001688:Biological Products; D006146:Guanidines; D006574:Heterocyclic Compounds, 2-Ring; C000592152:crambescin A2