New Cytotoxic Natural Products from the Red Sea Sponge Stylissa carteri

Author:

Abdelhameed Reda F. A.ORCID,Habib Eman S.,Eltahawy Nermeen A.,Hassanean Hashim A.,Ibrahim Amany K.,Mohammed Anber F.,Fayez ShaimaaORCID,Hayallah Alaa M.ORCID,Yamada Koji,Behery Fathy A.,Al-Sanea Mohammad M.,Alzarea Sami I.,Bringmann Gerhard,Ahmed Safwat A.,Abdelmohsen Usama RamadanORCID

Abstract

Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract’s metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC50 values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC50 at 36.8 ± 0.16 µM for 1 and IC50 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.

Publisher

MDPI AG

Subject

Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science

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