Alzarea Sami I, Elmaidomy Abeer H, Saber Hani, Musa Arafa, Al-Sanea Mohammad M, Mostafa Ehab M, Hendawy Omnia Magdy, Youssif Khayrya A, Alanazi Abdullah S, Alharbi Metab, Sayed Ahmed M, Abdelmohsen Usama Ramadan
Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia.
Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
Antibiotics (Basel). 2021 Apr 10;10(4):416. doi: 10.3390/antibiotics10040416.
LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae "Sargassaceae" dereplicated eleven compounds -. Further phytochemical investigation afforded two new aryl cresol -, along with eight known compounds -. Both new metabolites, along with 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 and were able to inhibit 5-LOX more preferentially than 15-LOX, while 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 and toward 5-LOX and 15-LOX.
液相色谱-质谱联用辅助的红海衍生褐藻“马尾藻科”代谢组学分析鉴定出11种化合物。进一步的植物化学研究得到了两种新的芳基甲酚，以及8种已知化合物。这两种新代谢物以及[未提及的物质]对肝癌细胞HepG2、乳腺癌细胞MCF-7和结肠癌细胞Caco-2均表现出适度的体外抗增殖活性。基于药效团的虚拟筛选表明，5-脂氧合酶（5-LOX）和15-脂氧合酶（15-LOX）是与其观察到的抗增殖活性最可能相关的靶点。体外酶活性测定表明，[未提及的物质]和[未提及的物质]对5-LOX的抑制作用比15-LOX更具选择性，而[未提及的物质]对两种酶均表现出趋同的抑制活性。进一步深入的计算机模拟研究揭示了两种酶活性位点内的分子相互作用，并解释了[未提及的物质]和[未提及的物质]对5-LOX和15-LOX的不同抑制活性。
