New glucose-6-phosphate dehydrogenase inhibitor from the Red Sea sponge Echinoclathria sp. (25th May 2021)

• Record Type: Journal Article
• Authors: F. A. Abdelhameed, Reda; Habib, Eman S.; Eltahawy, Nermeen A.; Hassanean, Hashim A.; Ibrahim, Amany K.; Fahim, John R.; Sayed, Ahmed M.; Hendawy, Omnia M.; Abdelmohsen, Usama R.; Ahmed, Safwat A.
• Is Part Of: Tetrahedron letters. Volume 72(2021)
• Publication Date: 2021-05-25
• Subjects: Echinoclathria sp. -- Echinosterol -- Thalassosterol -- In vitro cytotoxic activity -- Glucose-6-phosphate dehydrogenase -- Virtual screening -- Docking; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2021.152986
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Sponges of the genus Echinoclathria are a source of cytotoxic sterols. A new cytotoxic sterol, echinosterol with known one, thalassosterol were isolated. Glucose-6-phosphate dehydrogenase inhibition and proliferation of cancer cells. A comprehensive pharmacophore-based virtual screening was conducted. Docking and molecular dynamic simulation studies. Abstract: Chemical investigation of the methanol extract of the Red Sea sponge Echinoclathria sp ., led to the isolation of two pure compounds, one new sterol, named as (echinosterol), compound (1 ), along with known first reported sterol, (thalassosterol), compound (2 ). Structure elucidation was achieved using different spectroscopic techniques. The in vitro cytotoxic activity of the isolated compounds was tested against three human cancer cell lines, MCF-7, HepG2, and HeLa. Both compounds displayed strong to moderate cytotoxicity with IC50 values ranged from 3.23 to 28.1 µM. Subsequent pharmacophore-based virtual screening proposed glucose-6-phosphate dehydrogenase (G6PD) as the possible protein targets for both compounds, where they exhibited nanomolar inhibition (IC50 14.59 ± 0.77 and 23.86 ± 1.25, and K i 15.3 ± 1.11 and 9.6 ± 1.2 µM, respectively) upon the in vitro testing. Docking and molecular dynamic simulation studies were further illustrated the binding modes of both compounds inside the enzyme's active site.