title: Synthesis, structure and antitumor activity of new benz[d,e]isoquinoline-1,3-diones.
abstract: New benz[d,e]isoquinoline-1,3-diones related to mitonafide (CAS 54824-17-8) and amonafide (CAS 69408-81-7) with double substitution on the chromophore and branched side chains have been synthesized and their biological activity determined. Molecular modeling studies of 3a based on X-ray crystallographic data of mitonafide have shown that the aromatic system intercalates between GC steps of DNA. The in vitro cytotoxic test data using CX-1 and LX-1 cells showed higher cytotoxic activities in disubstituted derivatives compared to both lead compounds. Some of the compounds have been selected for in vivo test using L1210 tumor cells and CX-1 cells. Two of them (3b and 3j) have shown promising activity as good candidates for clinical development.
authors.affiliation: Knoll S.A., Madrid, Spain.
authors.forename: M F
authors.initials: MF
authors.lastname: Braña
authors.forename: J M
authors.initials: JM
authors.lastname: Castellano
authors.forename: M
authors.initials: M
authors.lastname: Morán
authors.forename: F
authors.initials: F
authors.lastname: Emling
authors.forename: M
authors.initials: M
authors.lastname: Kluge
authors.forename: E
authors.initials: E
authors.lastname: Schlick
authors.forename: G
authors.initials: G
authors.lastname: Klebe
authors.forename: N
authors.initials: N
authors.lastname: Walker
mesh_terms: D000225:Adenine; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D008968:Molecular Conformation; D053644:Naphthalimides; D063065:Organophosphonates; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D063065:Organophosphonates; C019215:mitonafide; C037020:amonafide; D000225:Adenine