Quantitative structure-activity relationship analysis of aryl alkanol piperazine derivatives with antidepressant activities

Quantitative structure-activity relationship analysis for recently synthesized aryl alkanol piperazine derivatives was studied for their antidepressant activities. The statistically significant 2D-QSAR models (r(2) > 0.924, r(-cv)(2) > 0.870, r(-pred)(2) > 0.890) were developed using genetic function approximation (GFA) when the number of descriptors in equation was set to four, indicating the descriptors of Atype_C_6, Dipole-mag, S_sssCH and Jurs-PNSA-3 mainly influence the 5-hydroxytryptamine (5-HT) reuptake inhibition activity while the descriptors of HOMO, PMI-mag, S_sssN and Shadow-XZ may chiefly control the noradrenaline (NA) reuptake inhibition activity. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by molecular field analysis (MFA), investigating the substitutional requirements for the favorable receptor-drug interaction and providing useful information in the characterization and differentiation of their binding sites. The results derived may be useful in further designing novel antidepressants prior to synthesis. (C) 2009 Elsevier Masson SAS. All rights reserved.