BIBLIOS

Document type
Journal articles

Document subtype
Full paper

Title
Application of Quantitative Structure-Activity Relationships to the Modeling of Antitubercular Compounds. 1. The Hydrazide Family.

Participants in the publication
C. Ventura (Author)
F. Martins. (Author)
Dep. Química e Bioquímica
CQB

Summary
A QSAR/QSPR methodology was used to analyze a set of 173 hydrazides, a great part of which are isoniazid (INH) derivatives. Nineteen molecular descriptors of various types (physicochemical, steric, geometrical,and electronic) have been systematically tested through a careful application of MLR. The analysis revealed that the biological activity of these compounds against M. tuberculosis does not depend on lipophilicity, as measured by log P. Properties that account for the biological response of isoniazid and related compounds,consistent with a mechanism involving the formation of radical species, were identified. The role of substituents in the stabilization of the intermediate species that gives rise to the active agent, the acyl radical,is discussed. It is postulated that the activation of INH derivatives’ prodrugs (hydrazines and hydrazones) occurs near the surface of M. tuberculosis.


Institution
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA

Where published
JOURNAL OF MEDICINAL CHEMISTRY

Publication Identifiers
ISSN - 0022-2623

Publisher
ACS Publications



Document Identifiers
DOI - https://doi.org/10.1021/jm701048s
URL - https://doi.org/10.1021/jm701048s

Rankings
SCIMAGO Q1 (2008) - 2.203 - Drug Discovery
Web Of Science Q1 (2008) - 4.898 - Medicinal Chemistry