Synthsis and antitumor properties of bis(quinaldine) derivatives.

ABSTRACT

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).