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-HT1A and 5-HT2A, serotonin receptor subtypes with the objective of designing more selective molecules for the 5-HT1A 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.

The picture illustrates the desirability obtained from two methodologies for the designed arylpiperazines with higher affinity to one of the receptors, revealing minor errors for the new methodology.Figure optionsDownload as PowerPoint slide