QSAR models for predicting the activity of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A using quantum chemical properties

Abstract

Multiple linear regression (MLR) combined with genetic algorithm (GA) and Bayesian-regularized Genetic Neural Networks (BRGNNs) were used to model the binding affinity (pKI) of 38 11,12-cyclic carbamate derivatives of 6-O-methylerythromycin A for the Human Luteinizing Hormone-Releasing Hormone (LHRH) receptor using quantum chemical descriptors. A multiparametric MLR equation with good statistical quality was obtained that describes the features relevant for antagonistic activity when the substituent at the position 3 of the erythronolide core was varied. In addition, four-descriptor linear and nonlinear models were established for the whole dataset. Such models showed high statistical quality. However, the BRGNN model was better than the linear model according to the external validation process. In general, our linear and nonlinear models reveal that the binding affinity of the compounds studied for the LHRH receptor is modulated by electron-related terms.

General structure and numbering of the 11,12-cyclic carbamate derivatives of 6-O-methylerythromycin A used in this study

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Correspondence to Julio Caballero.

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Fernández, M., Caballero, J. QSAR models for predicting the activity of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A using quantum chemical properties. J Mol Model 13, 465–476 (2007). https://doi.org/10.1007/s00894-006-0163-6

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Keywords

  • QSAR analysis
  • Bayesian-regularized Genetic Neural Network
  • Quantum chemical descriptors
  • Macrolide LHRH antagonists