Background: Seriniquinone (SQ – Fig 1) is a secondary metabolite isolated from a rare marine bacterium of the genus Serinicoccus, which has raised attention of the scientific community due to its specific action on skin protective antimicrobial peptide, dermcidin [1]. SQ is the only known natural product to bind and modulate such protein, which is over expressed in some cancer types and linked to a poor prognosis of such diseases [2]. The advance of this new bioactive molecule to drug development requires metabolism studies for the assessment of the potential of SQ to interact clinically with other drugs. In this context, this study aimed to evaluate the in vitro inhibitory effect of SQ on human CYP450. Methods: Specifics reactions catalyzed by CYP450 isoforms were monitored in the presence and absence of SQ (15 µM) using human liver microsomes and the inhibitory potential against the enzymes activities were determined. Furthermore, IC50 determinations were performed for the inhibited CYP450 isoforms. Results: The main CYP450 isoforms inhibited by SQ and its respective inhibition percentage were CYP1A2 (93%), CYP2E1 (65%), CYP3A4/5 (55% and 35% for midazolam 1’-hydroxylation and nifedipine oxidation reactions, respectively) and CYP2C19 (47%). Weak inhibition was observed for CYP2C9 (8%) and CYP2D6 was not inhibited. Conclusion : These results provide useful information about the safety of SQ as a drug candidate and suggest that its concomitant intake with drugs metabolized by CYP1A2, CYP2E1, CYP3A4/5 and CYP2C19 should be carefully monitored because it may lead to adverse SQ-drug interactions. Acknowledgments: We are grateful to FAPESP, CNPq and CAPES for financial support.
Fig 1. Chemical structure of seriniquinone (SQ)
References: [1] Trzoss L, Fukuda T, Costa-Lotufo LV, Jimenez P, La Clair JJ, Fenical W. Proc Nat Acad Sci USA 2014; 111: 14687-14692. [2] Bauer HA, D’arcy M, Libby TE, Thompson, HJ et al. Breast Cancer Res Treat 2014; 144: 299-306.