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Structure-property relationship for cellular accumulation of macrolones in human polymorphonuclear leukocytes (PMNs) (CROSBI ID 192282)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Munić Kos, Vesna ; Koštrun, Sanja ; Fajdetić, Andrea ; Bosnar, Martina ; Kelnerić, Željko ; Stepanić, Višnja ; Eraković Haber, Vesna Structure-property relationship for cellular accumulation of macrolones in human polymorphonuclear leukocytes (PMNs) // European journal of pharmaceutical sciences, 49 (2013), 2; 206-219. doi: 10.1016/j.ejps.2013.02.019

Podaci o odgovornosti

Munić Kos, Vesna ; Koštrun, Sanja ; Fajdetić, Andrea ; Bosnar, Martina ; Kelnerić, Željko ; Stepanić, Višnja ; Eraković Haber, Vesna

engleski

Structure-property relationship for cellular accumulation of macrolones in human polymorphonuclear leukocytes (PMNs)

Macrolones are a new class of antimicrobial compounds consisting of a macrolide scaffold linked to a 4-quinolone-3-carboxylic acid moiety via C(4″) position of a macrolide. As macrolides are known to possess favorable pharmacokinetic properties by accumulating in inflammatory cells, in this study we determined the intensity of accumulation in human polymorphonuclear leukocytes (PMNs) of 57 compounds of the macrolone class and analyzed the relationship between the molecular structure and this cellular pharmacokinetic property. Accumulation of macrolones ranged from 0 to 5.5-fold higher than the standard macrolide azithromycin. Distinct structural features in all three considered molecule parts: the macrolide scaffold, quinolone moiety and the linker, affect cellular accumulation. Interestingly, while the parent macrolide, azithromycin, accumulates approximately 3-fold more than clarithromycin, among macrolones all clarithromycin derivatives accumulated in PMNs significantly more than their azithromycin counterparts. Modeling cellular accumulation of macrolones with simple molecular descriptors, as well as with the measured octanol–water distribution coefficient, revealed that the number of hydrogen bond donors and secondary amide groups negatively contribute to macrolone accumulation, while lipophilicity makes a positive contribution.

macrolone; macrolide; quinolone; cellular accumulation; polymorphonuclear leukocyte (PMN); structure–property relationship (SPR)

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Podaci o izdanju

49 (2)

2013.

206-219

objavljeno

0928-0987

10.1016/j.ejps.2013.02.019

Povezanost rada

Kemija, Temeljne medicinske znanosti, Biologija

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