Application of desirability-based multi(bi)-objective optimization in the design of selective arylpiperazine derivates for the 5-HT1A serotonin receptor.
The multiobjective optimization technique based on the desirability estimation of several interrelated responses (MOOP-DESIRE) has been recently applied to quantitative structure-activity relationship (QSAR) studies. However, the advantage of applying this new methodology to the study of selectivity and affinity to competitive targets has been little explored. We used the MOOP-DESIRE methodology and a variation of this, to study the arylpiperazine derivates that could interact with 5-HT(1A) and 5-HT(2A), serotonin receptor subtypes with the objective of designing more selective molecules for the 5-HT(1A) receptor. We did show that the model results are in agreement with the available pharmacophore descriptions, guaranteeing an appropriate structural correlation and proving the methodology, as a useful tool for the important problem of selective drug design.
IBMC, Department of Biochemistry, Faculty of Pharmacy, University of Porto, 4150-047 Porto, Portugal. machadobq@gmail.com
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Machado
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Tejera
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Cruz-Monteagudo
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D015195:Drug Design; D008954:Models, Biological; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D011485:Protein Binding; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry*; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry*
D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A