Synthesis and mode(s) of action of a new series of imide derivatives of 3-nitro-1,8 naphthalic acid.
Four new imide derivatives of 3-nitro-1,8-naphthalic acid have been synthesised. The compounds show strong cytostatic activity against both HeLa and KB cells and are moderately toxic towards both mice and rats (LD50 above 4 mg/kg IP). Two of the most active compounds, M-4212 and M-12210, prevented the development of mouse Ehrlich ascites and rat Yoshida carcinoma. All these drugs block cell growth by inhibiting the synthesis of both DNA and RNA. In particular, both M-4212 and M-12210 raise the melting point of double-stranded DNA.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007094:Imides; D007546:Isoquinolines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use; D007928:Lethal Dose 50; D051379:Mice; D053644:Naphthalimides; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009574:Nitro Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use; D011759:Pyrrolidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D013055:Spectrophotometry, Infrared
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D009363:Neoplasm Proteins; D009574:Nitro Compounds; D011759:Pyrrolidines; C019215:mitonafide; C019222:pinafide; D012313:RNA