title: Studies on log Po/w of quinoxaline di-N-oxides: a comparison of RP-HPLC experimental and predictive approaches.
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 P(o/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.
authors.affiliation: Drug R&D Unit, Neglected Diseases Section, Center for Applied Pharmacobiology Research, University of Navarra, C/ Irunlarrea s/n, 31008 Pamplona, Spain. emoreno4@alumni.unav.es
authors.forename: Elsa
authors.initials: E
authors.lastname: Moreno
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gabano
authors.forename: Enrique
authors.initials: E
authors.lastname: Torres
authors.forename: James A
authors.initials: JA
authors.lastname: Platts
authors.forename: Mauro
authors.initials: M
authors.lastname: Ravera
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez-Silanes
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014376:Tuberculosis
chemical_list: D003497:Cyclic N-Oxides; D011804:Quinolines; D011810:Quinoxalines; C572588:quinoxaline-2-carboxamide-1,4-di-N-oxide