当前位置： SCI文献检索 > JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH期刊下所有文献 > Evaluation of naphthalmustine, a nitrogen mustard derivative of naphthalimide as a rationally-designed anticancer agent.

Evaluation of naphthalmustine, a nitrogen mustard derivative of naphthalimide as a rationally-designed anticancer agent.

Abstract：

:Naphthalmustine, 2-[2-[bis-(2-chloroethyl)amino]ethyl]-1H-benz[de]isoquinoline-1,3-dione (Compound 1) has been synthesized as a rationally designed new anticancer agent from N-(2-bromoethyl)naphthalimide. Its chemical alkylating activity exceeded that of nor-HN2 used as standard compound for comparison. Its antitumour efficacy was assessed in vivo in two murine ascites tumours namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. The clinical drug cyclophosphamide and the experimental compound mitonafide were used as positive controls for comparison. Compound 1 has displayed substantial and reproducible antitumoural activity in these tumours since very high remission times of treated animals were observed. Significant increase in the life span of mice bearing highly advanced tumour for 10 days before the drug challenge was also noted after its treatment. Its LD50 value was 200 mg/Kg by single i.p. injection. Its toxicity was also assessed in vivo in normal and in S-180 bearing mice by measuring drug-induced changes in hematological parameters, femoral bone marrow and splenic cellularity sequentially on days 9, 15 and 21 following drug treatment at the optimum dose of 12 mg/kg from day 1 to 7. The results indicated that the compound did not adversely affect hematopoiesis. Drug-induced hepatotoxicity and nephrotoxicity were also evaluated on those days but no such toxicities were detected. Naphthalmustine inhibits the synthesis of DNA and RNA in S-180 tumour cells. It was further screened in vitro in 4 different human tumour cell lines but no significant activity was observed in those lines.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Pain A,Samanta S,Dutta S,Saxena AK,Shanmugavel M,Kampasi H,Qazi GN,Sanyal U

keywords:

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

411-8

issue

3

eissn

0392-9078

issn

1756-9966

journal_volume

22

pub_type

杂志文章

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