Evaluation of beta-tethymustine, a new anticancer compound, in murine tumour models.
beta-Tethymustine, 1-[2- {bis(2'-chloroethyl)amino}ethyl]spiro[imidazolidine-4,2'-(1'H),3',4'-dihydronaphthalene]-2,5-dione, has been synthesised and LD50 value determined in Swiss male mice, which was found to be 100.00 mg/kg by single i.p. injection. The following three criteria, namely ascites cell count, ascites fluid measurement and increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice, were studied for evaluation of its antitumour efficacy in vivo in three murine ascites tumours, namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). At the optimum dose range of 8.0 mg/kg (higher) to 4.0 mg/kg (lower) for 1-7 days treatment following tumour transplantation on day 0, it exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and displayed excellent ILS(max) value of 80 in EAC, 224 in S-180 and 240 in DL, respectively, showing 'curative' effect (2-3/6 mice having 90 days survival rate). It also demonstrated a high ILS value of 150 with one cure/six mice bearing S-180 for 6 days prior to drug therapy. Screening results were compared with two clinical drugs, cyclophosphamide and 5-fluorouracil, serving as positive controls. Its chemical alkylating activity was compared with nor-HN2 (NSC 10873) and spiromustine (NSC 172112). The results indicate that it possesses greater alkylating activity than nor-HN2 and comparable activity with spiromustine.
Ghosh
M
M
Department of Chemotherapy, Chittaranjan National Cancer Institute, Calcutta 700 026, India.
Bhattacharya
S
S
Sadhu
U
U
Dutta
S
S
Sanyal
U
U
D000478:Alkylation / Q000187:drug effects; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D048289:Imidazolidines / Q000008:administration & dosage* / Q000737:chemistry; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage* / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D018906:Antineoplastic Agents, Alkylating; D048289:Imidazolidines; D009281:Naphthalenes; C119685:beta-tethymustine