title: Topological polar surface area: a useful descriptor in 2D-QSAR.
abstract: Topological polar surface area (TPSA), which makes use of functional group contributions based on a large database of structures, is a convenient measure of the polar surface area that avoids the need to calculate ligand 3D structure or to decide which is the relevant biological conformation or conformations. We demonstrate the utility of TPSA in 2D-QSAR for 14 sets of diverse pharmacological activity data. Even though a large pool of reports showing the importance of the classic 2D descriptors such as calculated logP (ClogP) and calculated molar refractivity (CMR) exists in the 2D-QSAR literature, this is the first report to demonstrate the value of TPSA as a relevant descriptor applicable to a large, structurally and pharmacologically diverse set of classes of compounds. We also address the limitations of applicability of this descriptor for 2D-QSAR analysis. We observed a negative correlation of TPSA with activity data for anticancer alkaloids, MT1 and MT2 agonists, MAO-B and tumor necrosis factor-alpha inhibitors and a positive correlation with inhibitory activity data for telomerase, PDE-5, GSK-3, DNA-PK, aromatase, malaria, trypanosomatids and CB2 agonists.
authors.affiliation: Department of Medicinal Chemistry, University of Mississippi, MS 38677-1848, USA.
authors.forename: S
authors.initials: S
authors.lastname: Prasanna
authors.forename: R J
authors.initials: RJ
authors.lastname: Doerksen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D014344:Trypanocidal Agents; D014409:Tumor Necrosis Factor-alpha