Bisdionin C-a rationally designed, submicromolar inhibitor of family 18 chitinases.

ABSTRACT: Chitinases of the GH18 family play important roles in a variety of pathogenic organisms and have also been shown to be involved in human asthma progression, making these enzymes potential drug targets. While a number of potent GH18 chitinase inhibitors have been described, in general, these compounds suffer from limited synthetic accessibility or unfavorable medicinal-chemical properties, making them poor starting points for the development of chitinase-targeted drugs. Exploiting available structural data, we have rationally designed bisdionin C, a submicromolar inhibitor of GH18 enzymes, that possesses desirable druglike properties and tractable chemical synthesis. A crystallographic structure of a chitinase-bisdionin C complex shows the two aromatic systems of the ligand interacting with

SUBMITTER: Schuttelkopf AW 

PROVIDER: S-EPMC4018065 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature