Faculty

Curriculum Vitae | Research Interests | Selected publications

Curriculum Vitae

• B.S., Physics, “Babeş-Bolyai” University, Cluj (Kolozsvár), Romania, 1986
• Ph.D., Pharmaceutics, University of Florida (advisor: Prof. Nicholas Bodor Ph.D., D.Sc.), 1997
• Postdoctoral Research Associate, Center for Drug Discovery, University of Florida, 1998-2000
• Senior Research Scientist, New Drug Development, IVAX Research, Inc., Miami, FL, 2000-2003
• Associate Director of Drug Discovery, New Drug Development, IVAX Research, Inc., Miami, FL, 2003-2006
• Assistant Professor, Department of Molecular and Cellular Pharmacology & Diabetes Research Institute, Miller School of Medicine, University of Miami, 2006-present

Research Interests

The general trend of my research is focused on the physicochemical and metabolic aspects of drug design and drug action and on the computer-aided quantitative modeling of various processes and phenomena. They cover a relatively wide range of fields including the prediction of various pharmaceutically-relevant properties by using quantitative structure-activity and structure-metabolism relationship (QSAR/QSMR) approaches; molecular modeling to characterize drug-receptor interactions and help drug candidate selection; computer-aided modeling of absorption, distribution, metabolism, excretion, and toxicity (ADMET) as well as pharmacokinetic (PK) data; and quantitative modeling and model selection criteria in general.

Quantitative structure-property relationship studies (QSPR, QSAR, and QSMR) aim to formulate a connection between chemical structure and some biological (or physicochemical) property of interest in quantifiable, mathematical terms. For example, we have shown that three-dimensional (3D) molecular size, as a descriptor that characterizes nonspecific interaction in liquids, has a determining influence on many properties of medicinal chemical relevance such as lipophilicity/hydrophobicity. Recently, the utility of this descriptor in describing data such as toxicity, antimicrobial activity, anticholinergic activity, and glucocorticoid receptor binding (Figure 1) has been further enhanced by combining it with a newly introduced, completely general bilinear model (LinBiExp), which was obtained starting from very general physicochemical considerations and by using a differential equation-based approach.





Figure 1 . The relative receptor-binding affinity (rRBA) of 6 α- or 9α-halogenated (or cyclic 16,17-ace tal containing) corticosteroids at the glucocorticoid receptor (GR) shows a bilinear trend as a function of molecular volume (on a logarithmic scale; left figure). Most highly active, marketed corticosteroids including, e.g., fluticasone propionate (magenta) or mometasone furoate (purple), are close to the ideal size and fit well within the ligand-binding domain of the human GR as their overlapping structures show (right figure).

Despite drug research being the main scientific factor driving the considerable medical progress of the last century, rational drug design (the development of effective pharmaceutical agents with minimal side effects on as rational a basis as possible) is still an elusive goal. Most new therapeutic agents designed to bind to a specific receptor or found to have high activity are, in the end, discarded mainly because of the unavoidable side effects or the unacceptable toxicities encountered in later stages of the development. The development of sufficiently predictive in silico models as well as the early integration of physicochemical, targeting, metabolism, and pharmacokinetic considerations into the drug design process is of crucial importance. Along these lines, we already developed fully computerized models to predict the rate of enzymatic hydrolysis, to generate and rank soft drug candidates within the framework of retrometabolic drug design, to establish in vitro-in vivo correlations (IVIVC), or to simultaneously describe parent and metabolite concentration data for a compound undergoing polymorphic N-acetylation.

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Selected Recent Publications

Buchwald, P. A general bilinear model to describe growth and decline time profiles.Math. Biosci.2006, Aug 25; Epub ahead of print.

Bodor, N. and Buchwald, P. Brain-targeted delivery of estradiol: therapeutic potential and results obtained with a chemical delivery system approach. Am. J. Drug Deliv.2006, 4, 161-175 (free full text of manuscript at http://www.cop.ufl.edu/centers/cdd/papers/braintargeteddelivery.pdf).

Buchwald, P. and Sveiczer, A. The time-profile of cell growth in fission yeast: model selection criteria favoring bilinear models over exponential ones.Theor. Biol. Med. Model. 2006, 3, 16 (free full text at http://www.tbiomed.com/content/3/1/16).

Bodor, N. and Buchwald, P. Corticosteroid design for the treatment of asthma: structural insights and the therapeutic potential of soft corticosteroids. Curr. Pharm. Des.2006, 12, 3241-3260.

Issar, M.; Sahasranaman, S.; Buchwald, P.; Hochhaus, G. Glucocorticoid to progesterone receptor selectivities of inhaled glucocorticoids. Eur. Resp. J. 2006, 27, 511-516.

Buchwald, P.; Einstein, B.; Bodor, N. QSAR study of 2,3-benzodiazepin-4(thi)one- and 1,2-phthalazine-related negative allosteric modulators of the AMPA receptor: a structural descriptors-based reassessment. QSAR Comb. Sci. , 2005, 24, 325-331.

Buchwald, P.; Juhász, A.; Bell, C.; Pátfalusi, M.; Howes, J.; Bodor, N. A pharmacogenetics-based unified parent–metabolite pharmacokinetic model incorporating acetylation polymorphism for talampanel in humans. J. Pharmacokinet. Pharmacodyn . 2005, 32, 377-400.

Buchwald, P. General linearized biexponential model for QSAR data showing bilinear-type distribution. J. Pharm. Sci. , 2005, 94, 2355-2379.

Wu, W.-M.; Buchwald, P.; Mori, N.; Ji, F.; Wu, J.-X.; Bodor, N. Pharmacokinetic and pharmacodynamic evaluation of the zwitterionic metabolite of a new series of soft anticholinergics. Pharm. Res. 2005, 22, 2035-2044 .

Ji, F.; Wu, W.-M.; Dai, X.; Mori, N.; Buchwald, P.; Bodor, N. Synthesis and pharmacological effect of new N-substituted soft anticholinergics based on glycopyrrolate. J. Pharm. Pharmacol. 2005, 57, 1427-1437.

Buchwald, P. and Bodor, N. Soft quaternary anticholinergics: comprehensive QSAR with a linearized biexponential (LinBiExp) model. J. Med. Chem.2006, 49, 883-891 (http://pubs.acs.org/cgi-bin/article.cgi/jmcmar/2006/49/i03/pdf/jm050679n.pdf).

Bodor, N. and Buchwald, P. Ophthalmic drug design based on the metabolic activity of the eye: soft drugs and chemical delivery systems. AAPS J.2005, 7, article 79 (E820-E833) (free full text at http://www.aapsj.org/articles/aapsj0704/aapsj070479/aapsj070479.pdf).

Buchwald, P. Direct, differential equation-based in vitro-in vivo correlation (IVIVC) method. J.Pharm. Pharmacol.2003, 55, 495-504.

Buchwald, P. and Bodor, N. Computer-aided drug design: The role of quantitative structure-property, structure-activity, and structure-metabolism relationships (QSPR/QSAR/QSMR). Drugs Future2002, 27, 577-588.

Buchwald, P. Complexation thermodynamics of cyclodextrins in the framework of a molecular size–based model for nonassociative organic liquids that includes a modified hydration-shell hydrogen-bond model for water. J. Phys. Chem. B2002, 106, 6864-6870.

Buchwald, P. Structure-metabolism relationships: steric effects and the enzymatic hydrolysis of carboxylic esters. Min. Rev. Med. Chem.2001, 1, 101-111.

Buchwald, P. and Bodor, N. Simple model for non-associative organic liquids and water. J. Am. Chem. Soc.2000, 122, 10671-10679.

Bodor, N. and Buchwald, P. Soft drug design: General principles and recent applications. Med. Res. Rev., 2000, 20, 58-101.

Buchwald, P. and Bodor, N. Quantitative structure-metabolism relationships: Steric and non-steric effects in the enzymatic hydrolysis of non-congener carboxylic esters. J. Med. Chem.1999, 42, 5160-5168.

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