Studies on Log P_o/w of Quinoxaline di-N-Oxides: A Comparison of RP-HPLC Experimental and Predictive Approaches.

Moreno, Elsa; Gabano, Elisabetta; Torres, Enrique; Platts, James A.; Ravera, Mauro; Aldana, Ignacio; Monge, Antonio; Pérez-Silanes, Silvia

As reported in our previous papers, a series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and studied as anti-tuberculosis agents. Here, the capability of the shake-flask method was studied and the retention time (expressed as log K) of 20 compounds were determined by RP-HPLC analysis. We found that the prediction of log P by the RP-HPLC analysis can result in a high accuracy and can replace the shake-flask method avoiding the experimental problems presented by quinoxaline di-N-oxides. The studied compounds were subjected to the ALOGPS module with the aim of comparing experimental log Po/w values and predicted data. Moreover, a preliminary in silico screening of the QSAR relationship was made confirming the influence of reduction peak potential, lipophilicity, H-bond donor capacity and molecular dimension descriptors on anti-tuberculosis activity.

QUINOXALINES; NITROGEN oxides; HIGH performance liquid chromatography; TUBERCULOSIS treatment; QSAR models; DRUG lipophilicity

Molecules, 2011, Vol 16, Issue 9, p7893

1420-3049

Academic Journal

10.3390/molecules16097893