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

Sami I Alzarea; Abeer H Elmaidomy; Hani Saber; Arafa Musa; Mohammad M Al-Sanea; Ehab M Mostafa; Omnia Magdy Hendawy; Khayrya A Youssif; Abdullah S Alanazi; Metab Alharbi; Ahmed M Sayed; Usama Ramadan Abdelmohsen

doi:10.3390/antibiotics10040416

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

Antibiotics (Basel). 2021 Apr 10;10(4):416. doi: 10.3390/antibiotics10040416.

Authors

Sami I Alzarea¹, Abeer H Elmaidomy², Hani Saber³, Arafa Musa^{4

5}, Mohammad M Al-Sanea⁶, Ehab M Mostafa^{4

5}, Omnia Magdy Hendawy^{1

7}, Khayrya A Youssif⁸, Abdullah S Alanazi^{9

10}, Metab Alharbi¹¹, Ahmed M Sayed¹², Usama Ramadan Abdelmohsen^{13

14}

Affiliations

¹ Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia.
² Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
³ Department of Botany and Microbiology, Faculty of Science, South Valley University, Qena 83523, Egypt.
⁴ Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
⁵ Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
⁷ Clinical Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, Egypt.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11371, Egypt.
⁹ Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia.
¹⁰ Health Sciences Research Unit, Jouf university, Sakaka 72341, Aljouf, Saudi Arabia.
¹¹ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
¹² Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt.
¹³ Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
¹⁴ Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, 7 Universities Zone, New Minia 61111, Egypt.

Abstract

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.

Keywords: 15-LOX; 5-LOX; Sargassum cinereum; aryl cresols; docking; in silico; metabolic profiling; virtual screening.

Grants and funding

375213500/The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for funding this work through the project number 375213500.