Type of Publication: | Journal article |
Publication status: | Published |
Author: | Globisch, Christoph; Pajeva, Ilza K.; Wiese, Michael |
Year of publication: | 2006 |
Published in: | Bioorganic & Medicinal Chemistry ; 14 (2006), 5. - pp. 1588-1598. - ISSN 0968-0896. - eISSN 1464-3391 |
Pubmed ID: | 16307883 |
DOI (citable link): | https://dx.doi.org/10.1016/j.bmc.2005.10.058 |
Summary: |
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.
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Subject (DDC): | 540 Chemistry |
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GLOBISCH, Christoph, Ilza K. PAJEVA, Michael WIESE, 2006. Structure–activity relationships of a series of tariquidar analogs as multidrug resistance modulators. In: Bioorganic & Medicinal Chemistry. 14(5), pp. 1588-1598. ISSN 0968-0896. eISSN 1464-3391. Available under: doi: 10.1016/j.bmc.2005.10.058
@article{Globisch2006-03Struc-38011, title={Structure–activity relationships of a series of tariquidar analogs as multidrug resistance modulators}, year={2006}, doi={10.1016/j.bmc.2005.10.058}, number={5}, volume={14}, issn={0968-0896}, journal={Bioorganic & Medicinal Chemistry}, pages={1588--1598}, author={Globisch, Christoph and Pajeva, Ilza K. and Wiese, Michael} }
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