Mass Spectrometry Analysis of Protonated Marine Natural Product Seriniquinone

Abstract

Seriniquinone is a natural quinone isolated from a rare marine bacterium of the genus Serinicoccus. This secondary metabolite has been shown to have anticancer properties, which has raised attention of the scientific community. In this short report, we present the first investigation of the gas-phase chemistry fragmentation reactions of seriniquinone in electrospray ionization tandem mass spectrometry (ESI-MS/MS), to be further applied in pharmacokinetics and metabolism studies. All the proposals herein were supported by computational chemistry.Keywords: Serinicoccus, seriniquinone, electrospray ionization mass spectrometry, quinones, computational chemistry IntroductionThe research regarding marine natural products have been responsible for the discovery of promising compounds for the treatment of several diseases, including good prototypes for cancer therapy.1 Seriniquinone (SQ, Figure 1), a metabolite isolated from a rare marine bacterium of the genus Serinicoccus, was recently characterized and evaluated for its cytotoxic activity.2 SQ belongs to a class of quinones, which is widely present in nature and is considered a target scaffold in medicinal chemistry as a gifted class of anticancer drugs.2 In vitro screening indicated that SQ is highly cytotoxic and selective towards eight out of the nine NCI 60 melanoma cells lines.2 Biochemical and pharmacological assessments demonstrated that SQ specifically targets a skin protective antimicrobial peptide, dermcidin, 2,3 which has also been described as a pro-survival protein in cancer cell lines. 4SQ is the only known natural product to bind and modulate such protein, and recent studies have reported dermcidin to be over expressed in some cancers types and linked to a poor prognosis of such disease. 5,6 In addition, studies have also shown that SQ induces autophagocytosis, further leading to an efficient elimination of cancer cells through apoptotic death. 2,7The advance of new bioactive molecules from natural sources to drug development requires preclinical evaluations, such as pharmacokinetic profile and metabolism studies, to answer basic safety questions concerning biomedical use of such compounds. [8][9][10] Serving such a purpose, liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is considered to be an important analytical technique for identification and quantification of the compounds of interest and their da Silva et al. 1163 Vol. 29, No. 5, 2018 metabolites.11 Besides the high sensitivity for analysis of small amount of substance in complex matrices, the combination of ESI and tandem or sequential mass spectrometry (MS/MS or MS n ) allows the reaction of a precursor ion with a non-reactive collision gas to obtain a fragmentation profile for this ion. ESI combined to collision-induced dissociation (CID) has already been applied for the rapid analysis of quinones, such as lapachol and naphthoquinone derivatives. 12,13 For an improved application of ESI-MS/MS technique, it is important to define the gas pha...

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