QSAR Models for Quinoxaline 1,4-di-n-oxide Derivatives as Antitrypanosomal Agents

E. VICENTE; P. R. DUCHOWICZ; S. PÉREZ-SILANES; I. ALDANA; E. A. CASTRO; H. CERECETTO; M. GONZÁLEZ; A. MONGE

Barcelona, España

Congreso; Frontiers in Medicinal Chemistry - Emerging Targets, Novel Candidates and Innovative Strategies; 2009

European Federation for Medicinal Chemistry

For the purpose of providing a rational guide for the synthesis of future compounds of this class, we established different Quantitative Structure-Activity Relationships (QSAR) with the available experimental biological data. First of all, we analyzed the effect of lipophilicity values on the activity of compounds through QSAR models, expressing the lipophilicity contribution with the octanol/water partition coefficient (logP). In addition, the molecular structure of twenty three quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives was appropriately represented by 1497 theoretical descriptors, calculated with Dragon software, and the best linear regression models established with our variable subset selection algorithm were predictive. Application of the QSAR equations developed now enables the proposal of new candidate structures that still do not have experimentally assigned biological data.