Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Shallow and Deep-water Ophiura Species Produce a Panel of Chlorin Compounds with Potent Photodynamic Anticancer Activities

Antonina Klimenko
,
Robin Huber
ORCID logo ,
Laurence Marcourt
ORCID logo ,
Dmitry Tabakaev
,
Alexey Koval
,
Salim Sh. Dautov
,
Tatyana N. Dautova
,
Jean-Luc Wolfender
* ORCID logo ,
Rob Thew
,
Yuri Khotimchenko
,
Emerson Ferreira Queiroz
* ORCID logo ,
Vladimir L. Katanaev
* ORCID logo
Version 1 : Received: 16 December 2022 / Approved: 22 December 2022 / Online: 22 December 2022 (05:02:21 CET)

A peer-reviewed article of this Preprint also exists.

Klimenko, A.; Huber, R.; Marcourt, L.; Tabakaev, D.; Koval, A.; Dautov, S.S.; Dautova, T.N.; Wolfender, J.-L.; Thew, R.; Khotimchenko, Y.; Queiroz, E.F.; Katanaev, V.L. Shallow- and Deep-Water Ophiura Species Produce a Panel of Chlorin Compounds with Potent Photodynamic Anticancer Activities. Antioxidants 2023, 12, 386. Klimenko, A.; Huber, R.; Marcourt, L.; Tabakaev, D.; Koval, A.; Dautov, S.S.; Dautova, T.N.; Wolfender, J.-L.; Thew, R.; Khotimchenko, Y.; Queiroz, E.F.; Katanaev, V.L. Shallow- and Deep-Water Ophiura Species Produce a Panel of Chlorin Compounds with Potent Photodynamic Anticancer Activities. Antioxidants 2023, 12, 386.

Abstract

A Pacific brittle star Ophiura sarsii has previously been shown to produce a chlorin (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) (1) 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 here identify five additional chlorin compounds from O. sarsii and its deep-sea relative O. ooplax: 10S-Hydroxypheophorbide a (2), Pheophorbide a (3), Pyropheophorbide a (4), (3S,4S,21R)-14-Ethyl-9-(hydroxymethyl)-21-(methoxycarbonyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (5), and (3S,4S,21R)-14-Ethyl-21-hydroxy-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (6). Chlorins 5 and 6 have not been previously reported in natural sources. Interestingly, low amounts of chlorins 1-4 and 6 could also be identified in a distant species, the basket star Gorgonocephalus cf. eucnemis, demonstrating that chlorins are produced by a wide spectrum of marine invertebrates of the class Ophiuroidea. Following purification of these major Ophiura chlorin metabolites, we discovered the high singlet oxygen quantum yield upon their photoinduction and their strong phototoxicity against a panel of cancer cell lines. These studies identify an arsenal of brittle star chlorins as powerful natural photosensitizers with potential photodynamic therapy applications.

Keywords

marine organisms; chlorins; photodynamic therapy; brittle stars; Ophiuroidea; phototoxicity; cancer

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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