Synthsis and antitumor properties of bis(quinaldine) derivatives.
A series of 7-nitro- and amino-N,'-bis(4-quinaldinyl)-alpha, omega-diaminoalkanes related to the 6-amino derivative 1 was synthesized and tested in the mouse P-388 lymphocytic leukemia screen. There of the 7-nitro derivatives (12, 14, and 15) were found to have moderate activity (T/C 140-150%), while other nitro derivatives (11 and 13) were devoid of any antitumor properties. All five 7-amino compounds (2-6) were moderately to strongly active (T/C 134-196%). In addition, binding of amino derivatives 2-6 to DNA was examined by their ability to (1) stabilize DNA to thermal denaturation and (2) inhibit the DNA-dependent RNA polymerase reaction in vitro. Tm data suggest that these compounds bind to DNA and are strong inhibitors of the polymerase reaction (I50 = 6-9 X 10(-6) M).
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D007942:Leukemia, Experimental / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D011798:Quinaldines / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D011804:Quinolines / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; D011798:Quinaldines; D011804:Quinolines; D004247:DNA; D012321:DNA-Directed RNA Polymerases