Abstract: The present invention provides novel bis-naphthalimides characterized by having a linker containing a heteroatom, their preparation, pharmaceutical compositions thereof, and various methods of using the bis-naphthalimides. Particularly preferred bis-naphthalimides have a linker of about 8-16 atoms where the heteroatom is oxygen, sulfur, sulfur oxide or sulfur dioxide. The bis-naphthalimides provided herein have exceptional DNA binding properties and demonstrate cytotoxicity in both in vitro and in vivo tumor models, in particular, against melanoma.
Type:
Grant
Filed:
July 22, 1994
Date of Patent:
February 18, 1997
Assignee:
Cancer Therapy & Research Center
Inventors:
Alexander L. Weis, Shih-Fong Chen, Peech S. Reedy, Mallaiah Mittakanti, Daniel L. Dexter
Abstract: The present invention provides novel bis-naphthalimides characterized by having a linker containing a heteroatom, their preparation, pharmaceutical compositions thereof, and various methods of using the bis-naphthalimides. Particularly preferred bis-naphthalimides have a linker of about 8-16 atoms where the heteroatom is oxygen, sulfur, sulfur oxide or sulfur dioxide. The bis-naphthalimides provided herein have exceptional DNA binding properties and demonstrate cytotoxicity in both in vitro and in vivo tumor models, in particular, against melanoma. Also provided a novel mono-naphthalimides linked to a DNA alkylating agent. These agents are shown to have conformational effects on double stranded DNA and to form covalent adducts after an extended incubation period.
Type:
Grant
Filed:
January 30, 1995
Date of Patent:
October 1, 1996
Assignee:
Cancer Therapy and Research Center
Inventors:
Alexander L. Weis, Shih-Fong Chen, Peech S. Reddy, Mallaiah Mittakanti, Daniel L. Dexter, Jan M. Woynarowski