title: Development of new CoMFA and CoMSIA 3D-QSAR models for anti-inflammatory phthalimide-containing TNFalpha modulators.
abstract: In the present study, we describe a new 3D-QSAR analysis of 42 previously reported thalidomide analogues, with the ability to modulate the pro-inflammatory cytokine TNFalpha, by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Three statistically significant models were obtained. The best resulting CoMFA and CoMSIA models have conventional r(2) values of 0.996 and 0.983, respectively. The cross-validated q(2) values are 0.869 and 0.868, respectively. The analysis of CoMFA and CoMSIA contour maps provided insight into the possible sites for structural modification of the thalidomide analogues for better activity and reduced toxicity.
authors.affiliation: Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, PO Box 68023, RJ 21944-970, Brazil.
authors.forename: Carolina Martins
authors.initials: CM
authors.lastname: Avila
authors.forename: Nelilma Correia
authors.initials: NC
authors.lastname: Romeiro
authors.forename: Gilberto M Sperandio
authors.initials: GM
authors.lastname: da Silva
authors.forename: Carlos M R
authors.initials: CM
authors.lastname: Sant'Anna
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010797:Phthalimides / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010797:Phthalimides; D014409:Tumor Necrosis Factor-alpha; C037431:phthalimide