Glucosidases inhibition

A different type of reactive bromo compound having a moderate resemblance to hexoses is represented by the bromoconduritols B (40) and F (41), named after the respective parent tetrahydroxycyclohexene. Even thou their hydroxylation pattern resembles that of D-glucose, only a few examples of D-glucosidase inhibition have been reported. The first was a-D-glucosi-dase from yeast, which is inhibited by bromoconduritol B (formerly called bromoconduritol A), having ki(max)/Kj 69,000 M" min", by alkylation of a histidine residue at the active site. 

Tabopda TK, Ngoupayo J, Awoussong PK, Mitaine-Offer AC, Ali MS, Ngadjui BT, Lacaille-Dubois MA. (2008) Triprenylated flavonoids from Dorstenia psilurus and their a-glucosidase inhibition properties. J Nat Prod 71 2068-2072. 

Fatty acid oxidation. Seeds, administered orally to rats at a dose of 200 g/kg, increased hepatic mitochondrial and the peroxisomal fatty acid oxidation rate " . Glucosidase inhibition. Ethyl acetate and water soluble fractions of the seed were inactive on the intestine " ... 

Johnston PS, Feig PU, Coniff RF, Krol A, Davidson JA, Haffner SM. Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring Hispanic NIDDM patients. Diabetes Care 1998 21(3) 409-15. 

Kameda Y, Asano N, Yoshikawa M, Takeuchi M, Yamaguchi T, Matsui K, Horii S, Fukase H (1984) Valiolamine, a new alpha-glucosidase inhibiting aminocyclitol produced by Streptomyces hygroscopicus. J Antibiot (Tokyo) 37 1301-1307... 

Matsui, T, Ueda, T., Oki, T, Sugita, K., Terahara, N., and Matsumoto, K. alpha-Glucosi-dase inhibitory action of natural acylated anthocyanins. 2. alpha-Glucosidase inhibition by isolated acylated anthocyanins, J. Agric. Food Chem., 49, 1952-1956, 2001. 

Another common mechanism of correction is ER glucosidase inhibition (Fig. 1, star 2), which prevents the recognition of misfolded proteins by calnexin and calreticulin and presumably allows them to escape the ERQC. Inhibition of glucosidase with castanospermine and miglustat were shown to correct the trafficking of deltaE508 CFTR and alpha-l-antitrypsin (51, 61). Whether this mechanism also works on other ER-retained mutants remains to be determined. 

Johnston PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL. Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. J Chn Endocrinol Metab 1998 83(5) 1515-22. 

Puls, W, Keup, U, Krause, H P, Thomas, G, Hoffmeister, E, Glucosidase inhibition. A new approach to the treatment of diabetes, obesity, and hyperlipoproteinemia, Naturwissenschaften, 64, 536-537, 1977. 

---