Find in Library

A Pacific brittle star <i>Ophiura sarsii</i> has previously been shown to produce a chlorin (3<i>S</i>,4<i>S</i>)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) (<b>1</b>) with potent phototoxic activities, making it applicable to photodynamic therapy. Using extensive LC-MS metabolite profiling, molecular network analysis, and targeted isolation with de novo NMR structure elucidation, we herein identify five additional chlorin compounds from <i>O. sarsii</i> and its deep-sea relative <i>O. ooplax</i>: 10S-Hydroxypheophorbide a (<b>2</b>), Pheophorbide a (<b>3</b>), Pyropheophorbide a (<b>4</b>), (3<i>S</i>,4<i>S</i>,21<i>R</i>)-14-Ethyl-9-(hydroxymethyl)-21-(methoxycarbonyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (<b>5</b>), and (3<i>S</i>,4<i>S</i>,21<i>R</i>)-14-Ethyl-21-hydroxy-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (<b>6</b>). Chlorins <b>5</b> and <b>6</b> have not been previously reported in natural sources. Interestingly, low amounts of chlorins <b>1</b>–<b>4</b> and <b>6</b> could also be identified in a distant species, the basket star <i>Gorgonocephalus</i> cf. <i>eucnemis</i>, demonstrating that chlorins are produced by a wide spectrum of marine invertebrates of the class Ophiuroidea. Following the purification of these major <i>Ophiura</i> chlorin metabolites, we discovered the significant singlet oxygen quantum yield upon their photoinduction and the resulting phototoxicity against triple-negative breast cancer BT-20 cells. These studies identify an arsenal of brittle star chlorins as natural photosensitizers with potential photodynamic therapy applications.