Thielavins A, J and K: α-Glucosidase Inhibitors from MEXU 27095, an Endophytic Fungus from Hintonia latiflora

Bioassay-guided fractionation of the active organic extract of MEXU 27095, an endophytic fungus isolated from the Mexican medicinal plant Hintonia latiflora, led to the separation of three tridepsides which were identified as thielavins A (1), J (2) and K (3). Compounds 1 – 3 inhibited Saccharomyces cerevisieae α-glucosidase (αGHY) in a non-competitive fashion (k_i's values 27.8, 66.2 and 55.4µM, respectively). The inhibitory action of 1 – 3 was higher than that of acarbose, used as positive control (k_i value of 156.1µM). Docking analysis predicted that 1 – 3 bind to αGHY (PDB code 3A4A) in a pocket close to the catalytic site. The α-glucosidase inhibitory properties of compound 3 were corroborated in vivo since it induced a noted antihyperglycemic action during an oral sucrose tolerance test in normal and diabetic mice. In addition, 3 provoked a moderate hypoglycemic activity in diabetic mice.