3D-quantitative structure activity analysis and quantum chemical analysis of pyrido-di-indoles

Abstract

The computational analyses of pyrido-di-indoles have been performed with various methods such as quantum mechanical studies (AM1, PM3, and DFT) and 3D-QSAR analyses (CoMFA and CoMSIA). The electrophilicity index along with some other properties has been related with biological activities. Electrostatic field has been identified as an important descriptor from the 3D-QSAR analyses. The AM1 geometry and Gasteiger-Marsili charged base CoMFA (r(predictive)(2) = 0.75) and CoMSIA (r(predictive)(2) 0.62) give strong correlation and indicate that a substitution at sites 2 and 3 of Ring A might affect the activity. In addition, a plausible statistical model has been found with DFT-based local philicity and negative Fukui function with a value of r(2) = 0.82 and r(cv)(2) = 0.60. The DFT analysis indicates that electron density of nitrogen atom of Ring B significantly contributes to activity. (C) 2007 Wiley Periodicals, Inc.