Automated Detection of Natural Halogenated Compounds from LC-MS Profiles–Application to the Isolation of Bioactive Chlorinated Compounds from Marine-Derived Fungi

Abstract

A collection of culture extracts obtained from several marine-derived fungal strains collected on the French Atlantic coast was investigated by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) in order to prospect for halogenated compounds and to identify potentially new ones. To achieve a fast, automated, and efficient data analysis, a bioinformatics tool named MeHaloCoA (Marine Halogenated Compound Analysis) was developed and included into R. After extraction of all the peaks from the metabolic fingerprints and their associated mass spectra, a mathematical filter based on mass isotopic profiles allowed the selective detection of halogenated (Cl and Br) molecules. Integrating MeHaloCoA into a dereplication approach allowed the identification of known and new halogenated compounds in a competitive amount of time. Subsequent targeted purification led to the isolation of several chlorinated metabolites, including two new natural products with bioactive potential, griseophenone I and chlorogriseofulvin, from a marine-derived Penicillium canescens strain.

Marine natural products

“…. The racemate of 5-chlorogriseofulvin has been synthesised but this is the rst isolation of (+)-5-chlorogriseofulvin 210 from a natural source (simultaneously obtained from Penicillium canescens below) 114 and although (+)-orthosporin has been obtained from a terrestrial fungus and (À)-orthosporin has been synthesised, the current report represents the rst isolation of (À)-orthosporin from a natural source. 113 The genus Aspergillus has again been well studied and has yielded many new metabolites.…”

“…166 A bioinformatics tool, MeHaloCoA (Marine Halogenated Compound Analysis) was developed and included in the soware R. Integration of the tool into a dereplication approach resulted in identication of known and new halogenated compounds including (+)-5-chlorogriseofulvin 210 (ref. 112) and griseophenone I 371 from Penicillium canescens 114. Chrysamides A-C 372-374 are dimeric nitrophenyl transepoxyamides obtained from Penicillium chrysogenum (deep sea sediment) of which 372 and 373 possess an unprecedented centrosymmetric dimer skeleton and 374 suppresses production of the pro-inammatory cytokine interleukin-17.…”

Marine-Derived Penicillium Species as Producers of Cytotoxic Metabolites

“…Using a bioinformatics tool, Marine Halogenated Compound Analysis (MeHaloCoA), three halogenated bioactive metabolites, (+)-5-chlorogriseofulvin ( 179 ) as well as griseophenones I and G ( 180 – 181 ), were isolated from a marine-derived P. canescens . They inhibited the growth of KB cells at a concentration of 0.6 μM (IR% = 49, 58, and 47%, respectively) [ 119 ]. Furthermore, one benzophenone, iso-monodictyphenone ( 182 ), and two diphenyl ether derivatives, penikellides A and B ( 183 – 184 ), were isolated from a mangrove endogenous fungus, Penicillium sp.…”

“…WC-29-5 Mangrove Phenolic polyketide H1975 3.97 μM [ 118 ] 178 Co-cultured Penicillium sp. WC-29-5 Mangrove Phenolic polyketide H1975, HL-60 (5.73, 3.73) μM [ 118 ] (+)-5-chlorogriseofulvin ( 179 ) P. canescens MMS460 Sea water Phenolic polyketide KB IR% (0.6 μM) = 49% [ 119 ] Griseophenone I ( 180 ) P. canescens MMS460 Sea water Phenolic polyketide KB IR% (0.6 μM) = 58% [ 119 ] Griseophenone G ( 181 ) P. canescens MMS460 Sea water Phenolic polyketide KB IR% (0.6 μM) = 47% [ 119 ] Iso-monodictyphenone ( 182 ) Penicillium sp...…”

Dynamic Cluster Analysis: An Unbiased Method for Identifying A + 2 Element Containing Compounds in Liquid Chromatographic High-Resolution Time-of-Flight Mass Spectrometric Data

“…Standards of Group-C were considered correctly classified if their molecular features were not present in the DCA-Hal and DCA-Sul analysis.The average correct classification for chemical features within a molecular feature of Group-Cl and Group-S standards was 87.5% for standards analyzed on the Bruker QTOF instrument, and 96.1% for standards analyzed on the Agilent QTOF instrument (SupportingTable S-5). comparative purposes the standards were also assessed using the MeHaloCoA method for halogen identification 10. As MeHaloCoA is not able to identify compounds containing sulfur nor is it able to identify multiply charged species, the direct comparison wasmade between singly charged chemical features identified by DCA-Hal with those found by the MeHaloCoA method.…”