Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds.
Four new ethylnitrosourea derivatives of substituted naphthalimides 3a-d have been synthesized from the respective N-(2-ethylamino) naphthalimides. Their chemical alkylating activity compared with the clinical drug CCNU and an experimental compound Mitonafide indicated that they possess lower alkylating activity than CCNU and comparable activity with the latter. Their anti-tumor efficacies were assessed in vivo in two murine ascites tumors 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. CCNU and Mitonafide were used as positive controls for comparison. The representative compound 3a has displayed marginal anti-tumoral activity in these tumors. Three compounds were further screened in vitro in 4 different human tumor cell lines but no significant activity was observed in those lines. These compounds moderately inhibit the synthesis of DNA and RNA in S-180 tumor cells.
Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Kolkata - 700026, India.
Anindita
A
Pain
Suva
S
Samanta
Sushanta
S
Dutta
Ajit K
AK
Saxena
Mutiah
M
Shanmugavel
Madhunika
M
Sharma
Gulam N
GN
Qazi
Utpal
U
Sanyal
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007094:Imides / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008130:Lomustine / Q000494:pharmacology; D051379:Mice; D053644:Naphthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects; D012510:Sarcoma 180 / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D018906:Antineoplastic Agents, Alkylating; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D009607:Nitrosourea Compounds; C019215:mitonafide; D012313:RNA; D008130:Lomustine; D004247:DNA