Klimenko Antonina, Huber Robin, Marcourt Laurence, Tabakaev Dmitry, Koval Alexey, Dautov Salim Sh, Dautova Tatyana N, Wolfender Jean-Luc, Thew Rob, Khotimchenko Yuri, Queiroz Emerson Ferreira, Katanaev Vladimir L
Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, CH-1206 Geneva, Switzerland.
Institute of Life Sciences and Biomedicine, Far Eastern Federal University, 690090 Vladivostok, Russia.
Antioxidants (Basel). 2023 Feb 5;12(2):386. doi: 10.3390/antiox12020386.
A Pacific brittle star has previously been shown to produce a chlorin (3,4)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) () 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 and its deep-sea relative : 10S-Hydroxypheophorbide a (), Pheophorbide a (), Pyropheophorbide a (), (3,4,21)-14-Ethyl-9-(hydroxymethyl)-21-(methoxycarbonyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (), and (3,4,21)-14-Ethyl-21-hydroxy-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (). Chlorins and have not been previously reported in natural sources. Interestingly, low amounts of chlorins - and could also be identified in a distant species, the basket star cf. , demonstrating that chlorins are produced by a wide spectrum of marine invertebrates of the class Ophiuroidea. Following the purification of these major 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.
先前已证明一种太平洋脆星能产生一种具有强大光毒性活性的二氢卟吩（3,4）-14-乙基-9-（羟甲基）-4,8,13,18-四甲基-20-氧代-3-卟吩丙酸（ETPA），使其适用于光动力疗法。通过广泛的液相色谱-质谱代谢物谱分析、分子网络分析以及利用从头核磁共振结构解析进行靶向分离，我们在此从该脆星及其深海近缘物种中鉴定出另外五种二氢卟吩化合物：10S-羟基脱镁叶绿酸a、脱镁叶绿酸a、焦脱镁叶绿酸a、（3,4,21）-14-乙基-9-（羟甲基）-21-（甲氧基羰基）-4,8,13,18-四甲基-20-氧代-3-卟吩丙酸以及（3,4,21）-14-乙基-21-羟基-9-（羟甲基）-4,8,13,18-四甲基-20-氧代-3-卟吩丙酸。二氢卟吩和尚未在天然来源中被报道过。有趣的是，在一个远缘物种——筐蛇尾cf.中也能鉴定出少量的二氢卟吩和，这表明二氢卟吩是由广泛的蛇尾纲海洋无脊椎动物产生的。在纯化这些主要的二氢卟吩代谢物后，我们发现它们光诱导后具有显著的单线态氧量子产率以及对三阴性乳腺癌BT-20细胞产生的光毒性。这些研究确定了一系列脆星二氢卟吩作为具有潜在光动力疗法应用的天然光敏剂。
