QSAR models for HEPT derivates as NNRTI inhibitors based on Monte Carlo method

• Computational investigation of HEPT derivates with anti-HIV-1 activity was carried out.
• Highly predictive models were obtained using Monte Carlo optimization method.
• SMILES and molecular graph based descriptors are calculated and applied.
• Structural indicators for increase and decrease of the IC50 are defined.
• New HEPT derivates with appropriate IC50 are proposed.

A series of 107 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio) thymine (HEPT) with anti-HIV-1 activity as a non-nucleoside reverse transcriptase inhibitor (NNRTI) has been studied. Monte Carlo method has been used as a tool to build up the quantitative structure–activity relationships (QSAR) for anti-HIV-1 activity. The QSAR models were calculated with the representation of the molecular structure by simplified molecular input-line entry system and by the molecular graph. Three various splits into training and test set were examined. Statistical quality of all build models is very good. Best calculated model had following statistical parameters: for training set r2 = 0.8818, q2 = 0.8774 and r2 = 0.9360, q2 = 0.9243 for test set. Structural indicators (alerts) for increase and decrease of the IC50 are defined. Using defined structural alerts computer aided design of new potential anti-HIV-1 HEPT derivates is presented.

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