Assessment of the relationship between the molecular properties of calcium channel blockers and plasma protein binding data

Jadranka V. Odović, Jovana B. Trbojević, Jasna B. Trbojević-Stanković, Dejan M. Nešić, Ratomir M. Jelić

Abstract


In this study we investigated the relationship between the calcium channel blockers (CCBs), amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem, and their calculated molecular descriptors: polar surface area (PSA), molecular weight (Mw), volume value (Vol), aqueous solubility data (logS), lipophilicity (logP), acidity (pKa values) and plasma protein binding (PPB) data, obtained from relevant literature. The relationships between the computed molecular properties of selected CCBs and their PPB data were investigated by simple linear regression analysis that revealed very low correlations (R2<0.35). When multiple linear regression (MLR) analysis was applied to investigate reliable correlations between the CCBs’ calculated molecular descriptors and PPB data, the best correlations were found for the relationships between CCBs, and PPB data and lipophilicity, and with application of the molecular descriptor (Mw, Vol, or pKa) data as additional independent variables (R2=0.623; R2=0.741; R2=0.657, respectively), with an acceptable probability value (P<0.05), confirming that lipophilicity, together with other molecular properties, are essential for the drugs’ PPB. We conclude that this could be considered as an additional in vitro approach for modeling CCBs.

DOI: 10.2298/ABS160609094O

Received: June 9, 2016; Revised: June 19, 2016; Accepted: June 21, 2016; Published online: October 7, 2016

How to cite this article: Odović JV, Trbojević JB, Trbojević-Stanković JB, Nešić DM, Jelić RM. Assessment of the relationship between the molecular properties of calcium channel blockers and plasma protein binding data. Arch Biol Sci. 2017;69(1):175-9.


Keywords


calcium channel blockers; hydrophobicity; molecular properties; lipophilicity; plasma protein binding

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