Marinoquinolones and Marinobactoic Acid: Antimicrobial and Cytotoxic ortho-Dialkylbenzene-Class Metabolites Produced by a Marine Obligate Gammaproteobacterium of the Genus Marinobacterium

Journal of Natural Products
2022.0

Abstract

Chemical investigation of the culture extract of a marine obligate proteobacterium, <i>Marinobacterium</i> sp. C17-8, isolated from scleractinian coral <i>Euphyllia</i> sp., led to the discovery of three new <i>o</i>-dialkylbenzene-class metabolites, designated marinoquinolones A (<b>1</b>) and B (<b>2</b>) and marinobactoic acid (<b>3</b>). Spectroscopic analysis using MS and NMR revealed the structures of <b>1</b> and <b>2</b> to be 4-quinolones with an <i>o</i>-dialkylbenzene-containing side chain at C3 and <b>3</b> to be a fatty acid bearing an <i>o</i>-dialkylbenzene substructure. The 4-quinolone form of <b>1</b> and <b>2</b> was unequivocally determined by comparison of the <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N chemical shifts of <b>1</b> with those predicted for 2-methyl-4-quinolone <b>A</b> and its tautomer 2-methyl-4-quinolinol <b>B</b> by quantum chemical calculation. Compound <b>1</b> was proven to be racemic by X-ray crystallographic analysis and chiral-phase HPLC analysis of its chemical degradation product. Compounds <b>1</b>-<b>3</b> exhibited antimicrobial activity against bacteria and filamentous fungi at MIC of 6.3-50 μg/mL. In addition, all compounds showed cytotoxicity against P388 murine leukemia cells at micromolar ranges.

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