Modelado de las relaciones cuantitativas estructura-actividad (QSAR) de los derivados 5-(nitroheteroaril)-1,3,4-tiadiazol con actividad leishmanicida

Abstract

In the present work a structure-activity relationship (QSAR) analysis for some derivatives of 5-(5-nitroheteroaryl)-1,3,4-thiadiazols with activity against protozoan Leishmania major; the main cause of leishmaniasis disease was performed. The set of descriptors used to build regression models were from electronic and topological nature, and derived from the density functional theory. QSAR models built enjoy a good statistical quality (R2 > 0,6 and Q2> 0,5) and were validated by cross-validation technique. Moreover, parameters were improved by using the jackknife regression technique. External validation of models showed a good predictive quality. We found that descriptors from the models indicate the increasing of dipole moment and hydrophobicity index tends to worsen the biological activity. Also, electrophilic power improves the effectiveness of 5-(5-nitroheteroaryl)-1,3,4-thiadiazols.The analysis showed that the reactivity nitro group present in these compounds is the most reactive derivative of such part.