QSAR Insights into Antidiabetic Activity of Natural Sulfur-Containing Compounds

Plants of the genus Salacia (Celastraceae) have long been used in traditional medical systems of South and Southeast Asia for the management of diabetes and related metabolic disorders. Modern phytochemical and pharmacological studies have confirmed the antidiabetic potential of several Salacia species, leading to the identification of a distinctive group of sulfur-containing sugars as their principal bioactive constituents. Salacinol, neosalacinol, kotalanol, neokotalanol, and related analogues represent a novel class of thiosugar sulfonium compounds that act as potent and selective α-glucosidase inhibitors, providing a clear mechanistic basis for their glucose-lowering effects. Simpler thiosugars, such as 5-thiomannose, further contribute to the overall metabolic activity of Salacia extracts and may serve as biosynthetic or functional precursors. Beyond Salacia, sulfur-containing natural products are widespread in nature and perform diverse biological roles. In particular, the genus Allium is well known for producing organosulfur compounds, including thioethers and polysulfides, which exhibit antidiabetic, hypolipidemic, antioxidant, and cardioprotective activities. In a different context, sulfur-containing hopanes have been identified in sediments and petroleum as products of early diagenetic sulfurization of bacterial hopanoids. Although these compounds have been studied primarily as geochemical biomarkers, recent QSAR/PASS analyses suggest that sulfur hopanes may also possess biologically relevant activities, particularly related to metabolic and cardiovascular regulation. Recent PASS-based QSAR evaluations of Salacia-derived thiosugars and sulfur hopanes predict significant antidiabetic activity, including potential type 2 diabetes-related pharmacological effects, supported by predicted α-glucosidase inhibitory, hypoglycemic, hepatic, and gastrointestinal activities. Collectively, these findings highlight sulfur-containing natural products from both plant and sedimentary sources as chemically diverse yet functionally convergent scaffolds with promising potential for the development of functional foods and therapeutic agents targeting metabolic disorders.