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ERIC Number: EJ946452
Record Type: Journal
Publication Date: 2011-Oct
Pages: 5
Abstractor: As Provided
Reference Count: 40
ISSN: ISSN-0021-9584
A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling
Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.
Journal of Chemical Education, v88 n10 p1389-1393 Oct 2011
Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to examine the factors that affect their ability to penetrate the blood-brain barrier. Seventy-eight molecules with known experimental log(BB) values [log(BB) = log(C[subscript brain]/C[subscript blood]), where C[subscript brain] and C[subscript blood] are the equilibrium molar concentrations of the drug molecule in the brain and the blood, respectively] were selected from the literature and their three-dimensional models constructed using the Spartan software program. For each molecule, the percent polarity was calculated using a space-filling model (PSA%, polar surface area percentage) and an electrostatic potential map that was constructed from the wave function obtained from a single-point energy calculation, using the EDF2 density functional model (PA%, polar area percentage). Plots of these ratios against the experimental log(BB) values clearly display the general trend that the blood-brain barrier penetration decreases as the extent of polarity of a molecule increases. These plots were used to examine the mechanisms for blood-brain barrier penetration by drug molecules belonging to a study set consisting of 10 CNS-active and 3 CNS-inactive drugs. Values of PSA% or PA% greater than [approximately equal to]15% favor uptake transporter or efflux transporter mediated molecular crossing of the blood-brain barrier. In addition, highly lipophilic drug molecules (PSA% or PA% less than [approximately equal to]10%) most likely cross the blood-brain barrier by passive diffusion. These results are in agreement with previous experimental studies. Given the relative ease of polar surface area ratio calculations, its influence on drug transports a suitable topic to include in undergraduate curriculum. Several instructional exercises have been included. (Contains 2 tables and 5 figures.)
Division of Chemical Education, Inc and ACS Publications Division of the American Chemical Society. 1155 Sixteenth Street NW, Washington, DC 20036. Tel: 800-227-5558; Tel: 202-872-4600; e-mail:; Web site:
Publication Type: Journal Articles; Reports - Research
Education Level: Higher Education
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A