Comparison of metabolism and activity of an aryldimethyltriazene and an aryldiethyltriazene

Biochem Pharmacol. 1986 Jan 15;35(2):209-15. doi: 10.1016/0006-2952(86)90515-0.

Abstract

The antitumoral activity and metabolism of 1-(4-acetylphenyl)-3,3-dimethyltriazene [pAc-(CH3)2] and 1-(4-acetylphenyl)-3,3-diethyltriazene [pAc-(C2H5)2] were studied in mice. pAc-(CH3)2 showed significant antitumoral activity against M5076 ovarian reticular cell sarcoma, L1210 leukemia, EL 4 lymphoma in mice, but not against Lewis lung carcinoma. pAc-(C2H5)2 was inactive in all these murine tumors and was much more toxic than pAc-(CH3)2. pAc-(CH3)2 and pAc-(C2H5)2 were rapidly metabolized in vitro and in vivo to their respective monoalkyltriazenes and to 4-aminoacetophenone (pAc-NH2). In vitro, 79% of the dimethyltriazene was metabolized to its monomethyl analogue, but only 27% of the diethyltriazene was metabolized to the monoethyltriazene. The monoalkytriazenes were almost completely biotransformed to pAc-NH2 by a 9000 g liver fraction. The metabolic pattern in the in vitro study was comparable to that found in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents*
  • Female
  • Leukemia L1210 / drug therapy
  • Lymphoma / drug therapy
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Neoplasm Metastasis
  • Neoplasms, Experimental / drug therapy*
  • Sarcoma, Experimental / drug therapy
  • Structure-Activity Relationship
  • Triazines / metabolism*
  • Triazines / therapeutic use
  • Triazines / toxicity

Substances

  • Antineoplastic Agents
  • Triazines