6533b826fe1ef96bd128474c

RESEARCH PRODUCT

Search of Chemical Scaffolds for Novel Antituberculosis Agents

subject

description

3 A method to identify chemical scaffolds potentially active against Mycobacterium tuberculosis is presented. The molecular features of a set of structurally heterogeneous antituberculosis drugs were coded by means of structural invariants. Three tech- niques were used to obtain equations able to model the antituberculosis activity: linear discriminant analysis, multilinear re- gression, and shrinkage estimation-ridge regression. The model obtained was statistically validated through leave-n-out test, and an external set and was applied to a database for the search of new active agents. The selected compounds were assayed in vitro, and among those identified as active stand reserpine, N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN), trifluoperazine, pentamidine, and 2-methyl-4,6-dinitro-phenol (DNOC). They show activity comparable to or superior to ethambutol, used in combination with other drugs for the prevention and treatment of Mycobacterium avium complex and drug-resistant tuberculosis. (Journal of Biomolecular Screening 2005:206-214)