Footprinting of inhibitor interactions of in silico identified inhibitors of trypanothione reductase of Leishmania parasite.

ABSTRACT: Structure-based virtual screening of NCI Diversity set II compounds was performed to indentify novel inhibitor scaffolds of trypanothione reductase (TR) from Leishmania infantum. The top 50 ranked hits were clustered using the AuPoSOM tool. Majority of the top-ranked compounds were Tricyclic. Clustering of hits yielded four major clusters each comprising varying number of subclusters differing in their mode of binding and orientation in the active site. Moreover, for the first time, we report selected alkaloids and dibenzothiazepines as inhibitors of Leishmania infantum TR. The mode of binding observed among the clusters also potentiates the probable in vitro inhibition kinetics and aids in defining key interaction which might contribute to the inhibition of enzymatic reduction of T[S] 2.

SUBMITTER: Venkatesan SK 

PROVIDER: S-EPMC3322522 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature