POTENT ANTITUMOR-ACTIVITY OF QUINOLONE COMPOUNDS WITH AN UNSATURATED AMINOAZABICYCLO GROUP AT THE C-7 POSITION OF THE QUINOLONE RING

Relationships between the substituents on the quinolone nucleus of 2 a nd related compounds and their biological activities were studied. 2, 3 and 1 carrying a (1R, 2R, 6R)-2-amino-8-azabicyclo[4.3.0.]non-3-en-8 -yl group at the C-7 position increased the rate of formation of DNA-p rotein complexes in cells, and inhibited the growth of tumor cells mor e strongly than the compounds with other substituents. The introductio n of a fluorine atom or a methoxy group at the 8-position and an amino group at the 5-position increased the activity still further. The thr ee compounds listed were all effective against P388 leukemia in mice. Subcutaneous injection of 2 at 2 mg/kg strongly suppressed the growth of human MX-1 breast cancer cells in nude mice. 1 has various function al groups that increase the cytotoxic potential of quinolone derivativ es: a (1R, 2R, 6R)-2-amino-8-azabicyclo[4.3.0.]non-3-en-8-yl moiety at C-7, a cyclopropyl group at the 1-position, fluorine atoms at the 6- and 8-positions, and an amino group at the 5-position of the quinoline carboxylic acid. These data suggest that this series of compounds pro vide good models for the further design of potent antitumor quinolones .