The correlation of plasma protein binding and molecular properties of selected antifungal drugs - Short Communication

Jadranka V. Odović, Milkica A Crevar Sakač, Zorica B Vujić


Antifungal agents are group of drugs commonly prescribed in tre­atment of fungal infections which are widely spread among global popu­lation. Their properties such as absorption, distribution, metabolism, route of elimi­na­tion or plasma protein binding (PPB), considerably influence their therapeutic success, while number of drug’s molecular physicochemical pro­perties notably influence all these processes. Lipophilicity (log P), mole­cular weight (Mw), volume (Vol), polar surface area (PSA) and solubility (log S) play important roles in drug absorption, penetration into tissues, distribution and route of eli­mination or the degree of plasma protein binding. In this study, the relation­ships between these five molecular properties of eight antifungal drugs and their plasma protein binding data obtained from relevant literature were inves­ti­gated. The drug’s selected physicochemical molecular descriptors were calcu­lated using software packages. The relationships between PPB and PSA; Mw; Vol and log S were established showing relatively poor correlation (r<0.35). The best correlation was obtained for the relationship between PPB data and lipophilicity descriptor X log P3 (correlation coefficient r = 0.55). In further in­vestigation, multiple linear regression analysis was applied. The best correla­tion was obtained with application of lipophilicity with polar surface area (r = 0.918) and volume (r = 0.916) or molecular weight (= 0.896) as inde­pendent variables.


Antimycotics; therapeutic success; lipophilicity; polar surface area; molecular weight; volume; solubility

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R. J. Perfect, Nat. Rev. Drug Discov. 16(9) (2017) 603 (https://doi:10.1038/nrd.2017.46 )

www. URL: (date accessed 19. 09. 2019.)

J. E. Nett, D. R. Andes, Infect. Dis. Clin. North Am. 30(1) (2016) 51 (

M. A. Ghannoum, L.B. Rice, Clin. Microbiol. Rev. 12(4) (1999) 501 (https://doi:10.1128/CMR.12.4.501)

R. Bellmann, Curr. Clin. Pharmacol. 2(1) (2007) 37 (

M. Schäfer-Korting, H. C. Korting, F. Amann, R. Peuser, A. Lukacs, Antimicrob. Agents. Chemother. 35(10) (1991) 2053 (https://doi:10.1128/AAC.35.10.2053)

H. J. Schmitt, J. Andrade, F. Edwards, Y. Niki, E. Bernard, D. Armstrong, Eur. J. Clin. Microbiol. Infect. Dis. 9(11) (1990) 832 (

N. S. Ryder, L. Frank, J. Med. Vet. Mycol. 30(6) (1992) 451 (

D. Gonzalez, S. Schmidt, H. Derendorf, Clin. Microbiol. Rev. 26(2) (2013) 274 (

M. Schäfer-Korting M, H. C. Korting, W. Rittler, W. Obermüller, Infection. 23(5) (1995) 292 (

J. Kujawski, H. Popielarska, A. Myka, B. Drabinska, M. Bernard, CMST. 18(2) (2012) 81 (

T. L. Lemke, D. A. Williams, The Foye's Principles of Medicinal Chemistry, 7th ed. Lippincott Williams & Wilkins, Philadelphia, USA, 2013 (ISBN-13: 978-1-6091-3345-0)

A. C. Moffat, M. D. Osselton, B. Widdop, Clarke’s Analysis of Drugs and Poisons 4th ed., Pharmaceutical Press, London, UK, 2011 (ISBN 978-0-8536-9711-4) URL: (date accessed 19. 09. 2019.) URL: (date accessed 19.09.2019.) URL: (date accessed 19.09.2019.)

Y. H. Zhao, J. Le, M. H. Abraham, A. Hersey, P. J. Eddershaw, C. N. Luscombe, D. Boutina, G. Beck, B. Sherbone, I. Cooper, J. A. Platts, J. Pharm. Sci. 90 (2001) 749 (

Y. H. Zhao, M. H. Abraham, J. Le, A. Hersey, C. N. Luscombe, G. Beck, B. Sherborne, I. Cooper, Pharmac. Res. 19(10) (2002) 1446 (

R. Mannhold, G. I. Poda, I. V. Tetko, J. Pharm. Sci. 98 (2009) 861 ( )

R. Estrada-Tejedor, N. Sabaté, F. Broto, S. Nonell, Afinidad. 70(564) (2013) 250 (

A.G. Asuero, A. Sayago, A.G. Gonzalez, Crit. Rev. Anal. Chem. 36 (2006) 41 (

E.H. Kerns, L. Di, Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization. Elsevier, San Diego, California USA, 2008 (ISBN: 978-0-1236-9520-8)


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