Multiple Linear Regression Study of 2,4-Disubstituted 1,5-Benzodiazepine as Potential Antiinfectives

Abstract

<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 11.5pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;"> This paper describes 3D-QSAR analysis and biological evaluation of 1,5-benzodiazepine analogues. Benzodiazepine nucleus with its simple structure gives a good opportunity for further modification regarding an increase of its antimicrobial activity. We synthesized a series of benzodiazepine analogues from condensation of various chalcones and halo substituted o-phenelynene diamines. All compounds were assayed <em>in vitro</em> against, <em>E. coli</em>, <em>P. aeruginosa</em>, <em>S. aureus</em>. The models were generated on the Vlife MDS 3.5; selected models showed a correlation coefficient (r</span>^{<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 16pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">2</span>}<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 11.5pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">) above 0.9 with cross-validated correlation coefficient (q</span>^{<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 16pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">2</span>}<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 11.5pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">) above 0.8, respectively, for all the selected organisms. The 3D-QSAR models generated were externally validated for all models using a test set of 6 molecules for which the predictive r</span>^{<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 16pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">2</span>}<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 11.5pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;"> (r</span>^{<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 16pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">2</span>}<span style="line-height: 115%; font-family: 'Times New Roman','serif'; font-size: 11.5pt; mso-fareast-font-family: 'Times New Roman'; mso-fareast-theme-font: minor-fareast; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">-pred) was found to be above 0.45. The results of 3D-QSAR indicate that contours can be used to design some potent antibacterial agents.</span>