Assessment of the relationship between the molecular properties of calcium channel blockers and plasma protein binding data
Keywords:
calcium channel blockers, hydrophobicity, molecular properties, lipophilicity, plasma protein bindingAbstract
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.
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.
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Beale JM, Block JH. Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry. 12th ed. Philadelphia: Wolters Kluwer, Lippincott Williams and Wolters; 2011. 1010 p.
Lemke TL, Williams DA. The Foye’s Principles of Medicinal Chemistry. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. 1500 p.
Moffat AC, Osselton MD, Widdop B, editors. Clarke’s Analysis of Drugs and Poisons. 4th ed. London: Pharmaceutical Press; 2011.
Stella VJ, Borchardt RT, Hageman MJ, Oliyai R, Maag H, Tilley JW. Biotechnology: Pharmaceutical Aspects, Prodrugs: Challenges and Rewards. 18th ed. New York: Springer Science, Business Media; 2007.
Sweetman, SC. Martindale: The Complete Drug Reference. 36th ed. London: Pharmaceutical Press; 2009.
Di L, Kernsy EH. Profiling drug-like properties in discovery research. Curr Opin Chem Biol. 2003;7:402-8.
Hartmann T, Schmitt J. Lipophilicity – beyond octanol/water: a short comparison of modern technologies. Drug Discov Today Techn. 2004;1(4):431-9.
Remko M, Swart M, Bickelhaupt FM. Theoretical study of structure, pKa, lipophilicity, solubility, absorption and polar surface area of some centrally acting antihypertensives. Bioorg Med Chem. 2006;14:1715-28.
Remko M. Acidity, lipophilicity, solubility, absorption, and polar surface area of some ACE inhibitors. Chem Pap. 2007;61(2):133-41.
Zhao YH, Le J, Abraham MH, Hersey A, Eddershaw PJ, Luscombe CN, Boutina D, Beck G, Sherbone B, Cooper I, Platts JA. Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. J Pharm Sci. 2001;90:749-84.
Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Met. 2000;44:235-49.
Christiaans JAM, Windhorst AD, Groenenberg PM, van der Goot H, Timmerman H. Synthesis and in vitro pharmacology of new 1,4-dihydropyridines. 1. 2-(ω-Aminoalkylthiomethyl) - 1, 4 - dihydropyridines as potent calcium channel blockers. Eur J Med Chem. 1993;28(11):859-67.
Kalavagunta PK, Bagul PK, Jallapally A, Kantevari S, Banerjee SK, Ravirala N. Design and green synthesis of 2-(diarylalkyl) aminobenzothiazole derivatives and their dual activities as angiotensin converting enzyme inhibitors and calcium channel blockers. Eur J Med Chem. 2014;83:344-54.
Pozo ED, Baeyens JM. Effects of calcium channel blockers on neuromuscular blockade induced by aminoglycoside antibiotics. Eur J Pharmacol. 1986;128(1-2):49-54.
Sepehr-Ara L, Mohajeri SA, Mahmoudian M. Effect of the two new calcium channel blockers mebudipine and dibudipine on vascular flow of isolated kidney of normal and diabetic rats. Pathophysiology. 2011;18(3);175-84.
Whyte I, Buckley N, Dawson A. Calcium channel blockers. Medicine. 2012; 40(3):112-14.
Mayama C. Calcium channels and their blockers in intraocular pressure and glaucoma. Eur J Pharmacol 2014;739:96-105.
Odovic J, Trbojevic-Stankovic J. Correlation between Angiotensin-converting enzyme inhibitors lipophilicity and protein binding data. Acta Medica Medianae. 2012;51(4):13-8.
Odovic J, Vladimirov S, Karljikovic-Rajic K. In Vitro modeling of angiotensin-converting enzyme inhibitor's absorption with chromatographic retention data and selected molecular descriptors. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;953-954:102-7.
Trbojević-Stanković J, Odović J, Jelić R, Nešić D, Stojimirović B. The influence of certain molecular descriptors of fecal elimination of angiotensin II receptor antagonists. Arch Biol Sci. 2015;67(1):103-9.
Trbojević-Stanković J, Odović J, Jelić R, Nešić D, Stojimirović B. The effect of calcium channel blockers’ molecular properties on elimination route. Arch Biol Sci. 2015;67(3):801-6.
Trbojević J, Odović J, Trbojević-Stanković J, Nešić D, Jelić R. Relationship between the bioavailability and molecular properties of angiotensin ii receptor antagonists. Arch Biol Sci. 2016;68(2):273-8.
Asuero AG, Sayago A, Gonzalez AG. The correlation coefficient: An overview. Crit Rev Anal Chem. 2006;36:41-59.
Martin PD, Warwick MJ, Dane AL, Hill SJ, Giles PB, Phillips PJ, Lenz E. Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers. Clin Ther. 2003;25(11):2822-35.
Verho M, Luck C, Stelter WJ, Rangoonwala B, Bender N. Pharmacokinetics, metabolism and biliary and urinary excretion of oral ramipril in man. Curr Med Res Opin. 1995; 13(5):264-73.
Odović JV, Markovic BD, Trbojević-Stanković JB, Vladimirov SM, Karljiković RKD. Evaluation of ACE inhibitors lipophilicity using in silico and chromatographically obtained hydrophobicity parameters. Hem Ind. 2013;67(2):209-16.
Mannhold R, Poda GI, Tetko IV. Calculation of molecular lipophilicity: state-of-the-art and comparison of log P methods on more than 96,000 compounds. J Pharm Sci. 2009;98:861-93.
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