Comparison of metabolism and activity of an aryldimethyltriazene and an aryldiethyltriazene.
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.
D000818:Animals; D000970:Antineoplastic Agents; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012513:Sarcoma, Experimental / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014227:Triazines / Q000378:metabolism* / Q000627:therapeutic use / Q000633:toxicity
D000970:Antineoplastic Agents; D014227:Triazines