[Quantitative aspects of the relationship of the antitumor activity and toxicity of diaziridinyl-sym. triazines to their physicochemical properties].
The experiments on rats have shown that there is a linear dependence of the logarithms of reciprocal molar toxic (LD50) and therapeutic (ED50) for sarcoma 45 doses of 6-oxyalkyl-amino-2,4-bis(I-aziridinyl)-sym-triazines and 6-(5-substituted-2,2-dimethyl-1,3-dioxan-5-yl)-amino-2,4-bis(I-aziridinyl)-sym-triazines upon the induction constants of substituents at tertiary carbon, the antitumor activity being more sensitive to the substituent effect compared with the toxicity. The dependence of the logarithms of reciprocal molar therapeutic (ED50 for sarcoma 45 and ED95 for Walker sarcoma) and toxic (LD50 and LD100) doses of the compounds, both synthesized by us and taken from the literature, upon the logarithms of their distribution coefficients in the octanol-water system (IgP) shows a parabolic character with the maximum effect at the extreme point of the parabola. The antitumor activity was more sensitive to a changed IgP than the toxicity.
D000818:Animals; D000970:Antineoplastic Agents; D001388:Aziridines / Q000627:therapeutic use / Q000633:toxicity*; D001389:Azirines / Q000633:toxicity*; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007928:Lethal Dose 50; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014227:Triazines / Q000627:therapeutic use / Q000633:toxicity*
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D014227:Triazines
Kolichestvennye aspekty sviazi protivoopukholevoĭ aktivnosti i toksichnosti diaziridinil-simm. triazinov s ikh fiziko-khimicheskimi svoĭstvami.