en بيوشيمي بالینی Biochemistry پژوهشي Research <div style="text-align: justify;"><span style="font-size:12pt"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><b><u><span style="line-height:115%"><span style="color:#2f5496">Background & Objectives:</span></span></u></b> Alkaloids constitute a structurally diverse class of naturally occurring compounds with a wide range of pharmacological activities. One of the principal mechanisms through which alkaloids may contribute to the management of diabetes mellitus (DM) is the inhibition of &alpha;-glucosidase. Despite their considerable therapeutic potential, the molecular interactions between alkaloids and &alpha;-glucosidase remain insufficiently characterized and warrant comprehensive investigation. Therefore, this study aimed to identify potential alkaloid-derived &alpha;-glucosidase inhibitors using an <em>in silico</em> approach for the management of DM.</span></span></span><br> <span style="font-size:12pt"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><b><u><span lang="EN" style="line-height:115%"><span style="color:#2f5496">Materials & Methods:</span></span></u></b> An initial computational screening of 15 alkaloid ligands excluded cepharanthine because of predicted mutagenicity and immunotoxicity, whereas tetrandrine and fangchinoline were excluded because they failed to satisfy drug-likeness criteria. The remaining 12 compounds were subsequently subjected to molecular docking against &alpha;-glucosidase.</span></span></span><br> <span style="font-size:12pt"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><b><u><span lang="EN" style="line-height:115%"><span style="color:#2f5496">Results:</span></span></u></b> Scopolamine exhibited the most favorable docking score (-6.91 kcal/mol), outperforming acarbose, the reference inhibitor (-6.87 kcal/mol). In the &alpha;-glucosidase and scopolamine complex, Arg699 and Glu301 participated in hydrogen bond and Pi anion interactions, respectively. Secondary structure analysis further revealed scopolamine induced conformational alterations in &alpha;-glucosidase, characterized by an increase in &alpha;-helix content and a reduction in &beta;-sheet content, changes that were consistent with its predicted inhibitory activity.<span lang="EN" style="line-height:115%"></span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:115%"><span style="font-family:&quot;Times New Roman&quot;,serif"><b><u><span lang="EN" style="line-height:115%"><span style="color:#2f5496">Conclusion:</span></span></u></b><b> </b>These findings suggest that scopolamine is a promising candidate &alpha;-glucosidase inhibitor. Nevertheless, further <em>in vitro</em> and <em>in vivo</em> studies are required to validate its antidiabetic potential and determine its therapeutic value for controlling postprandial hyperglycemia in DM.<b><span style="line-height:115%"></span></b></span></span></span></div> Alkaloids, α-glucosidase inhibition, Diabetes mellitus, Scopolamine, In silico. 0 0 http://jabs.fums.ac.ir/browse.php?a_code=A-10-2208-4&slc_lang=en&sid=1 Mohsen Keshtmand محسن کشتمند mohsenkest45@gmail.com 100319475328460030861 0009-0009-9387-1342 No Department of Biochemistry, Sa.C., Islamic Azad University, Sanandaj, Iran گروه بیوشیمی، دانشکده علوم پزشکی، واحد سنندج، دانشگاه آزاد اسلامی، سنندج، ایران Morteza Sadeghi مرتضی صادقی ms.biochemistry2015@gmail.com 100319475328460030862 100319475328460030862 Yes Department of Biochemistry, Sa.C., Islamic Azad University, Sanandaj, Iran گروه بیوشیمی، دانشکده علوم پزشکی، واحد سنندج، دانشگاه آزاد اسلامی، سنندج، ایران