Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae Sargassum cinereum : An In-Silico-Supported In-Vitro Study.

Autor: Alzarea SI; Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia., Elmaidomy AH; Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt., Saber H; Department of Botany and Microbiology, Faculty of Science, South Valley University, Qena 83523, Egypt., Musa A; Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.; Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt., Al-Sanea MM; Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia., Mostafa EM; Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.; Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt., Hendawy OM; Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia.; Clinical Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, Egypt., Youssif KA; Department of Pharmacognosy, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11371, Egypt., Alanazi AS; Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia.; Health Sciences Research Unit, Jouf university, Sakaka 72341, Aljouf, Saudi Arabia., Alharbi M; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia., Sayed AM; Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt., Abdelmohsen UR; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.; Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, 7 Universities Zone, New Minia 61111, Egypt.
Jazyk: angličtina
Zdroj: Antibiotics (Basel, Switzerland) [Antibiotics (Basel)] 2021 Apr 10; Vol. 10 (4). Date of Electronic Publication: 2021 Apr 10.
DOI: 10.3390/antibiotics10040416
Abstrakt: LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae Sargassum cinereum "Sargassaceae" dereplicated eleven compounds 1 - 11 . Further phytochemical investigation afforded two new aryl cresol 12 - 13 , along with eight known compounds 14 - 21 . Both new metabolites, along with 19, showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed 12 and 13 were able to inhibit 5-LOX more preferentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes' active sites and explained the varying inhibitory activity for 12 and 13 toward 5-LOX and 15-LOX.
Databáze: MEDLINE