Plakortinic Acids A and B: Cytotoxic Cycloperoxides with a Bicyclo[4.2.0]octene Unit from Sponges of the Genera <i>Plakortis</i> and <i>Xestospongia</i>

Plakortinic acids A (<b>2</b>) and B (<b>3</b>), two polyketide endoperoxides with a bicyclo[4.2.0]­octene unit, were isolated as minor constituents from the sponge–sponge symbiotic association <i>Plakortis halichondrioides</i>–<i>Xestospongia deweerdtae</i>, along with known epiplakinic acid F (<b>1</b>). The structures of the mixture of two inseparable compounds were determined by spectroscopic analysis. Screening for cytotoxic activity of the mixture against two human tumor cell lines revealed that these compounds are very active at sub-micromolar concentration

Exploring the Sponge Consortium <i>Plakortis symbiotica–Xestospongia deweerdtae</i> as a Potential Source of Antimicrobial Compounds and Probing the Pharmacophore for Antituberculosis Activity of Smenothiazole A by Diverted Total Synthesis

Fractionation of the bioactive CHCl₃–MeOH (1:1) extracts obtained from two collections of the sponge consortium <i>Plakortis symbiotica</i>–<i>Xestospongia deweerdtae</i> from Puerto Rico provided two new plakinidone analogues, designated as plakinidone B (<b>2</b>) and plakinidone C (<b>3</b>), as well as the known plakinidone (<b>1</b>), plakortolide F (<b>4</b>), and smenothiazole A (<b>5</b>). The structures of <b>1</b>–<b>5</b> were characterized on the basis of 1D and 2D NMR spectroscopic, IR, UV, and HRMS analysis. The absolute configurations of plakinidones <b>2</b> and <b>3</b> were established through chemical correlation methods, VCD/ECD experiments, and spectroscopic data comparisons. When assayed in vitro against <i>Mycobacterium tuberculosis</i> H₃₇Rv, none of the plakinidones <b>1</b>–<b>3</b> displayed significant activity, whereas smenothiazole A (<b>5</b>) was the most active compound, exhibiting an MIC value of 4.1 μg/mL. Synthesis and subsequent biological screening of <b>8</b>, a dechlorinated version of smenothiazole A, revealed that the chlorine atom in <b>5</b> is indispensable for anti-TB activity