CP-MLR directed QSAR studies on the antimycobacterial activity of functionalized alkenols—topological descriptors in modeling the activity

Abstract

The antimycobacterial activity of nitro/acetamido alkenol derivatives and chloro/amino alkenol derivatives has been analyzed through combinatorial protocol in multiple linear regression (CP-MLR) using different topological descriptors obtained from Dragon software. Among the topological descriptor classes considered in the study, the activity is correlated with simple topological descriptors ( TOPO) and more complex 2D autocorrelation descriptors ( 2DAUTO). In model building the descriptors from other classes, that is, empirical, constitutional, molecular walk counts, modified Burden eigenvalues, and Galvez topological charge indices have made secondary contribution in association with TOPO and/or 2DAUTO classes. The structure–activity correlations obtained with the TOPO descriptors suggest that less branched and saturated structural templates would be better for the activity. For both the series of compounds, in 2DAUTO the activity has been correlated to the descriptors having mass, volume and/or polarizability as weighting component. In these two series of compounds, however, the regression coefficients of the descriptors have opposite arithmetic signs with respect to one another. Outwardly these two series of compounds appear very similar. But in terms of activity they belong to different segments of descriptor–activity profiles. This difference in the activity of these two series of compounds may be mainly due to the spacing difference between the C1 (also C6) substituents and rest of the functional groups in them.