Evaluation of ACE inhibitors lipophilicity using in silico and chromatographically obtained hydrophobicity parameters/Procena lipofilnosti ace inhibitora primenom in silico i hromatografski dobijenih parametara hidrofobnosti

• Published in: Hemijska industrija 2013-03, Vol.67 (2), p.209
• Main Authors: Odovic, Jadranka V, Markovic, Bojan D, Trbojevic-Stankovic, Jasna, Vladimirov, Sote M, Karljikovic-Rajic, Katarina D
• Format: Article
• Language: English
• Subjects: Analysis; Chromatography; Lisinopril; Quinapril
• ISSN: 0367-598X
• DOI: 10.2298/HEMIND120522078O

The aim of this study was to compare different calculation methods to determine the lipophilicity, expressed as log P value, of seven ACE inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril and benazepril) with significantly different structures. Experimentally determined n-octanol/water partition coefficients, log [P.sub.O/W] values, were obtained from relevant literature. The correlations between all collected log P values were studied and the best agreement between calculated log P and experimentally determined log [P.sub.O/W] values was observed for KOWWINlog P or Milog P values (r = 0.999 or r = 0.974, respectively). The correlations between all collected log P values and chromatographically (reversed-phase thin-layer chromatography) obtained hydrophobicity parameters, [R.sub.M.sup.0] and [C.sub.0], were established. Good correlations (r > 0.90) were obtained in the majority of relationships. The KOWWINlog P was established as the most suitable hydrophobicity parameter of the investigated group of ACE inhibitors with r = 0.981 for correlation with [R.sub.M.sup.0] and r = = 0.977 for correlation with [C.sub.0] parameters (water-methanol mobile phase). Using multiple linear regressions, it was established that application of two selected log P, calculated by different mathematical approaches, led to very good correlation due to the benefits of both calculation methods. The good relationships indicate that the computed log P, with careful selection of method calculation, can be useful in ACE inhibitors lipophilicity evaluation, as a high-throughput screening technique. Keywords: Lipophilicity, ACE inhibitors, hydrophobicity parameters, reversed-phase thin-layer chromatography, computed log P. U radu je analizirana lipofilnost sedam ACE inhibitora (enalapril, kvinapril, fosinopril, lizinopril, cilazapril, ramipril i benazepril) razlicitih hemijskih struktura. Primenom programskih paketa izracunato je deset razlicitih deskriptora lipofilnosti, log P vrednosti, za ispitivane ACE inhibitore dok su njihovi eksperimentalno odredeni n-oktanol/voda koeficijenti raspodele (log [P.sub.O/W]) preuzeti iz strucne literature. Izmedu izracunatih log P vrednosti uocene su znacajne razlike zbog razlika u primenjenim metodama izracunavanja. Ispitane su korelacije izmedu svih log P vrednosti. Najbolje slaganje je dobijeno izmecu eksperimentalnih log [P.sub.O/W] i izracunatih KOWWINlog P (r = 0,999) ili Milog P vrednosti (r = 0,974). Analiziran je