Studies on Log Pow of Quinoxaline di-N-Oxides A Comparison of RP-HPLC Experimental and Predictive Approaches 英文参考文献.docVIP

Molecules 2011, 16, 7893-7908; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Studies on Log Po/w of Quinoxaline di-N-Oxides: A Comparison of RP-HPLC Experimental and Predictive Approaches Elsa Moreno 1,2,*, Elisabetta Gabano 2, Enrique Torres 1, James A. Platts 3, Mauro Ravera 2, Ignacio Aldana 1, Antonio Monge 1 and Silvia Pérez-Silanes 1 1 Neglected Diseases Section, Drug RD Unit, Center for Applied Pharmacobiology Research, University of Navarra, C/ Irunlarrea s/n, 31008 Pamplona, Spain 2 Dipartimento di Scienze dell’Ambiente e della Vita, Università del Piemonte Orientale “A. Avogadro”, Viale Michel 11, 15121 Alessandria, Italy 3 School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK * Author to whom correspondence should be addressed; E-Mail: emoreno4@alumni.unav.es; Tel.: +34-948-425653; Fax: +34-948-425652. Received: 30 August 2011; in revised form: 6 September 2011 / Accepted: 7 September 2011 / Published: 13 September 2011 Abstract: 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. Keywords: H