Structure-activity relationships of a series of tariquidar analogs as multidrug resistance modulators.
Tariquidar (XR9576) analogs, modulators of cancer multidrug resistance ( MDR), were subjected to QSAR and 3D-QSAR analyses. The structural features contributing to anti- MDR activity were identified by the Free-Wilson analysis and pharmacophore search using Hoechst 33342 as a template. 3D-QSAR CoMFA and CoMSIA models were derived and tested. The best models yielded an external predictivity of 0.66-0.75 squared correlation coefficient and outlined HB-acceptor, steric, and hydrophobic fields as the most important 3D properties. On the basis of the QSAR and 3D-QSAR analyses it was suggested that the strong inhibitory potency of the compounds studied is related to the presence of a bulky aromatic ring system with a 3rd positioned heteroatom toward the anthranilamide nucleus in the opposite end of the tetrahydroquinoline group. The results can help in directing the rational design of new generations of potent P-glycoprotein MDR modulators.[1]References
- Structure-activity relationships of a series of tariquidar analogs as multidrug resistance modulators. Globisch, C., Pajeva, I.K., Wiese, M. Bioorg. Med. Chem. (2006) [Pubmed]
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