Synthesis and antitumor activity of halogen-substituted 4-(3,3-dimethyl-1-triazeno)quinolines.
Halogenated 4-(3,3-dimethyl-1-triazeno)quinolines were synthesized as potential antitumor agents on the basis of the biochemical pharmacological properties of existing triazenes, their structural-activity relationships, and the high melanin binding of chloroquine and iodoquine in vivo and in vitro. They were synthesized by diazotization of appropriate halogen-substituted 4-aminoquinolines in fluoboric acid at -5 degrees C followed by coupling with dimethylamine. Among these new compounds, 8-chloro-4-(3,3-dimethyl-1-triazeno)quinoline produces significant antitumor activity against both P-388 and L1210 murine leukemias. Although only marginally active or inactive against P-388, the other chloro, bromo, or iodo analogues show activity against L1210 comparable to that of dacarbazine (DIC). However, none of these compounds is active against B-16 melanoma. Compared with DIC these new agents demonstrate a higher in vitro affinity for melanin; however, this affinity is apparently not correlated with their antitumor activity.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011804:Quinolines / Q000138:chemical synthesis / Q000627:therapeutic use*; D014226:Triazenes / Q000138:chemical synthesis / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D008543:Melanins; D011804:Quinolines; D014226:Triazenes