Comparative QSAR studies on substituted bis-(acridines) and bis-(phenazines)-carboxamides: a new class of anticancer agents.
Quantitative structure-activity relationships have been formulated for two sets of DNA binding topoisomerase agents (bis-acridines and bis-phenazines) acting on murine P388 leukemia cells, murine Lewis lung carcinoma (LL(C)) cells and human Jurkat leukemia wild-type (JL(C)) cells. For the acridines, all three QSARs (1-3) show only a (small negative) hydrophobic effect. In sharp contrast, the phenazines in all three studies (4-6) show a strong hydrophobic effect, with the optimum ClogP being near 7.3 for all examples. This suggests that, despite the structural similarity of the compounds, different modes of enzyme and/or DNA binding may be involved.
Garg
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Chemistry Department, Pomona College, Claremont, CA 91711-6338, USA. rngarg@pomona.edu
Denny
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Hansch
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D000166:Acridines / Q000737:chemistry* / Q000494:pharmacology; D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000609:Aminoacridines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D019281:Dimerization; D006801:Humans; D020128:Inhibitory Concentration 50; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D010619:Phenazines / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000166:Acridines; D000577:Amides; D000609:Aminoacridines; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D010619:Phenazines; D059004:Topoisomerase I Inhibitors; C062948:N-((2-dimethylamino)ethyl)-9-aminoacridine-4-carboxamide