In silico investigation of the relation between calcium channel blockers’ molecular descriptors and oral bioavailability data

Abstract

Calcium channel blockers are commonly prescribed antihypertensive drugs. In this study, nine calcium channel blockers (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem) were investigated to evaluate the relationship between their molecular properties and oral bioavailability data collected from relevant literature. Several molecular descriptors of calcium channel blockers: lipophilicity descriptors, different logP values (AlogPs, AClogP, AB/logP, milogP, AlogP, MlogP, KOWWINlogP, XLOGP2, XLOGP3), aqueous solubility data (logS), electronic descriptor - polar surface area (PSA), constitutional parameter - molecular weight (Mw), geometric descriptor - volume value (Vol), acidity descriptor (pKa) were calculated using different software packages. The relationships between computed molecular descriptors and literature-obtained oral bioavailability data were firstly investigated using simple linear regression analysis showing relatively poor correlations with R 2 & 0.6. In continuation, multiple linear regression was applied to achieve higher correlation between calcium channel blockers’ oral bioavailability and their molecular properties, on the first place lipophilicity and one additional, molecular descriptor. The best correlations were established between calcium channel blockers’ oral bioavailability and their lipophilicity data (milogP or KOWWINlogP) with application of acidity descriptor as additional independent variable (R 2 = 0.783 and R 2 = 0.826). Application of computed molecular descriptors in evaluating drugs bioavailability was checked on three additional, fourth generation CCBs, cilnidipine, lacidipine, lercandipine.