Hypoglycemic activity and metabolite diversity of Archangium sp. UTMC 4535 with the first report on magnodelavin biosynthesis by bacteria.

Abstract

Diabetes has been declared an epidemy by the World Health Organization and represents a significant metabolic comorbidity. Given the promising pharmaceutical activities of myxobacterial secondary metabolites, we investigated the inhibitory potential of compounds from the soil myxobacterium Archangium sp. UTMC4535, leading to the identification of magnodelavin C, a guaiane sesquiterpene lactone.This study details the isolation, structural elucidation, and biological evaluation of magnodelavin C against enzymes associated with type 2 diabetes (T2D), specifically alpha (α)-glucosidase and glucose transferase, utilizing molecular docking and in vitro assessments. Docking studies identified five binding pockets in α-glucosidase, with magnodelavin C displaying favorable binding scores between -5.4 to -6.7 kcal/mol. Experimental results indicated that magnodelavin C inhibited α-glucosidase approximately three times more effectively than the crude extract, exhibiting potency comparable to the standard drug acarbose. Furthermore, magnodelavin C demonstrated an inducing effect on glucose transport with an average uptake percentage of 80 % compared to the drug control. MTT assay results confirmed that magnodelavin C exhibited no cytotoxic effects on the L929 fibroblast cell line at any tested concentration, contrasting with acarbose's approximately 25 % mortality rate. This compound also demonstrated advantageous drug-likeness properties and human intestinal absorption while exhibiting lower toxicity compared to acarbose. The discovery of magnodelavin C highlights the rich diversity of secondary metabolites produced by myxobacteria and their potential applications in drug discovery.