QSAR, phenothiazines

Contrary to the results of most quantitative structure-activity relationship (QSAR) studies on phenothiazine type modulators, Dearden et al. [195] found that molecular size, polarity, or polarizability better than other structural features of the compounds correlated with MDR reversing ability, P-gp associated ATPase activity, and inhibition of drug efflux from the blood-brain barrier. They did not find evidence that hydrogen bonding or hydrophobicity played a role in MDR reversal. 

Abstract Quantitative structure-activity relationship (QSAR) analysis for minimum inhibitory concentration (MIC) of phenothiazines and benzo[a]phenothiazines was investigated based on the theoretical calculations. Four different dipole moments (/jq, /xesp g, /zw, and /zesp-w) and heats of formation (AHf) of the phenothiazines [1-20], benzo [n]phenothiazines [21-29], and benz[c]acridines [30-41] were separately calculated in the gas-phase and the water-solution by the conductor-like screening model/parametric method 3 (COSMO/PM3) technique. The MIC values of phenothiazines [1-20] were well correlated to A AHf, HOMO energy and hq. QSAR may be applicable to predict the MIC of phenothiazines. 

Keywords Benz[c] acridines Benzo [a] phenothiazines Biological activity Phenothiazines QSAR Theoretical calculations... 

CH2-CH2-N-CH2-CH2 (179), and linear discriminant analysis with topological descriptors (180). In 1997 the first 3D-QSAR (quantitative structure-activity relationships) analysis of phenothiazines and related drugs known to be P-gp inhibitors was described... 

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