Alanzi Abdullah R, Parvez Mohammad K, Alqahtani Moneerah J, Al-Dosari Mohammed S
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Saudi Pharm J. 2023 Nov;31(11):101776. doi: 10.1016/j.jsps.2023.101776. Epub 2023 Aug 30.
Chronic diabetes mellites related hyperglycemia is a major cause of mortality and morbidity due to further complications like retinopathy, hypertension and cardiovascular diseases. Though several synthetic anti-diabetes drugs specifically targeting glucose-metabolism enzymes are available, they have their own limitations, including adverse side-effects. Unlike other natural or marine-derived pharmacologically important molecules, deep-sea fungi metabolites still remain under-explored for their anti-diabetes potential. We performed structure-based virtual screening of deep-sea fungal compounds selected by their physiochemical properties, targeting crucial enzymes viz., α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B involved in glucose-metabolism pathway. Following molecular docking scores and MD simulation analyses, the selected top ten compounds for each enzyme, were subjected to pharmacokinetics prediction based on their AdmetSAR- and pharmacophore-based features. Of these, cladosporol C, tenellone F, ozazino-cyclo-(2,3-dihydroxyl-trp-tyr), penicillactam and circumdatin G were identified as potential inhibitors of α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B, respectively. Our data therefore, warrants further experimental and pharmacological studies to validate their anti-diabetes therapeutic potential.
慢性糖尿病相关的高血糖是导致死亡和发病的主要原因，因为它会引发诸如视网膜病变、高血压和心血管疾病等进一步的并发症。尽管有几种专门针对葡萄糖代谢酶的合成抗糖尿病药物，但它们都有各自的局限性，包括不良副作用。与其他天然或海洋来源的具有重要药理作用的分子不同，深海真菌代谢产物的抗糖尿病潜力仍未得到充分探索。我们对根据其物理化学性质选择的深海真菌化合物进行了基于结构的虚拟筛选，目标是参与葡萄糖代谢途径的关键酶，即α-淀粉酶、α-葡萄糖苷酶、胰腺脂蛋白脂肪酶、己糖激酶-II和蛋白酪氨酸磷酸酶-1B。根据分子对接分数和分子动力学模拟分析，对每种酶选择的前十种化合物，基于其AdmetSAR和药效团特征进行药代动力学预测。其中，枝孢醇C、细交链孢菌酮酸F、氮杂环丁烷-环-(2,3-二羟基-色氨酸-酪氨酸)、青霉内酰胺和环达汀G分别被鉴定为α-淀粉酶、α-葡萄糖苷酶、胰腺脂蛋白脂肪酶、己糖激酶-II和蛋白酪氨酸磷酸酶-1B的潜在抑制剂。因此，我们的数据需要进一步的实验和药理学研究来验证它们的抗糖尿病治疗潜力。
