Studies on alpha-Glucosidase Inhibitors Development: Magic Molecules for the Treatment of Carbohydrate Mediated Diseases

• Type: Another Publication in an International Scientific Journal
• Date: 2012

Authors

Moorthy, NSHN (Author) Other; Ramos, MJ (Author) FCUP; Fernandes, PA (Author) FCUP

Journal

Title: Mini-Reviews in Medicinal Chemistry

Vol. 12

Pages: 713-720

ISSN: 1389-5575

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 46 Citations

Scopus - 54 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-8HZ

DOI: 10.2174/138955712801264837

Abstract (EN): alpha-Glucosidase (EC 3.2.1.20) enzyme belongs to the glycosidase family enzymes, cleave the glycosidic bond of the oligosaccharides that liberate glucose and its inhibition retards the carbohydrate digestion. In the present review, we have discussed the structural features of different alpha-glucosidase inhibitors (small molecules) responsible for the inhibitory activities. The reported computational studies including, QSAR, pharmacophore modelling, homology models, docking (with analogs enzymes), etc revealed that the topological, electronic and hydrophobicity properties determine the interactions of those molecules. The aromatic substituents connected with flexible bonds in the molecules have significant effect on the interactions, which may due to the presence of aromatic amino acid residues in the active site. The reported homology modelled and other analogs enzymes (enzymes of other species) also confirmed the existence of aromatic residue (amino acids) especially, histidine, phenylalanine and tyrosine in their active site along with the polar (glutamic and aspartic acids) residues. Multiple sequence alignments of the alpha-glucosidase enzymes (from different species) described that the abovementioned amino acid residues are present in the active site of all the studied enzymes. Recently, Celgosivir (MIGENIX Inc) is an oral prodrug of the natural product castanospermine used for the treatment of HCV infection by inhibiting alpha-glucosidase I. BMN-701 is an alpha-glucosidase inhibitors in the phase I pipeline (BioMarine) for the treatment of Pompe diseases. CKD-711 and CKD-711a are aminooligosaccharide alpha-glucosidase inhibitors and the in vitro study of CKD-711 showed similar effects to acarbose on porcine intestinal maltase and sucrase (IC(50)s of 2.5 and 0.5 mu g/ml). This review also concluded that many alpha-glucosidases inhibitors obtained from natural products are used for the treatment of various carbohydrate mediated diseases. The structural analysis of these synthetic and natural derivatives guide for the development of novel semisynthetic/synthetic alpha-glucosidase inhibitors with free of toxicities.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8