Drug Design by Regression Analyses of Newly Synthesized Derivatives of 8-Quinolinol

ABSTRACT

The aim of the present study was to establish a relationship between antibacterial activities of newly synthesized derivatives of 8-Quinolinol and their structure. To accomplish the latter, the minimal inhibitory concentrations (MIC, mg/dm³) of the investigated compounds against Staphylococcus aureus were determined and applied in the mathematical model.

Twenty four substituted derivatives of 8-Quinolinol, with general formula: were tested through regression analysis and their MIC were determined and compared to reference strain of Staphylococcus aureus. A linear model for the relationship between the biological activity expressed as—ln(1.MIC⁻¹) and the structure of the compounds described by descriptors reflecting electronic, steric and thermodynamic parameters was proposed. A selection of descriptors having the greatest impact on biological activity was performed by stepwise regression:

—ln(1.MIC⁻¹)=0.503135+0.650967ClogP—0.00991Tot.E—0.000001Bind—0.014489MR+0.001922G+0.000028E+ 0.292877LUMO

A correlation between the antimicrobial activity of the resulting compounds and some selected descriptors with the coefficient of determination R² = 0.988 was established. Its high value defined the model as adequate and proved its high predictive ability. The resulting regression equation allowed the prediction of the antimicrobial activity of new not synthesized derivatives of 8-Quinolinol.

Keywords:

• 8-Quinolinol
• Staphylococcus aureus
• drug design
• mathematical model
• QSAR