Quantitative Analysis of the Structure–Activity Relationship for Cyclooxygenase-2 Inhibitors Based on Diarylheterocyclic Derivatives

A quantitative analysis of the structure–activity relationship for cyclooxygenase-2 (COX-2) inhibitors, which are diarylheterocyclic derivatives, was performed using the GUSAR 2019 program. In this work, QSAR models were constructed using the pIC₅₀ parameter [log(1/IC₅₀)], where IC₅₀ (expressed in mmol/L) is the concentration of the drug that inhibits 50% of the enzyme activity. The experimental values of the IC₅₀ parameter for the simulated compounds ranged from 1.00–9549.93 nmol/L. Nine statistically significant consensus models were developed for predicting the numerical IC₅₀ values. These models demonstrate satisfactory prediction accuracy for the pIC₅₀ parameter for both the structures used in the training data and for two independent test sets and CHEMBL129021, CHEMBL339798, CHEMBL285831 suggests the potential use of models M1–M9 for the virtual screening of virtual libraries and databases to find new potentially efficient inhibitors of COX-2. A combination of MNA (Multilevel Neighborhoods of Atoms) and QNA (Quantitative Neighborhoods of Atoms) descriptors with three whole molecular descriptors (topological length, topological volume and lipophilicity) was used to develop 9 statistically significant, valid consensus QSAR models.