Antitumor activity of Nitronaphthal-NU, a novel mixed-function agent.
Nitronaphthal-NU (Compound 1) was synthesized as a mixed-function antitumor agent based on the structures of the clinical drug CCNU and experimental compound Mitonafide. In vitro screening in four human tumor cell lines namely SNB-78 CNS, HOP-62 Lung, T47D Breast and SiHa - cervix revealed significant cytotoxicity in the former two cell lines much greater than CCNU and comparable to Mitonafide used as standards. In vivo antitumoral potency assessed in the murine ascites tumors Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times of drug treated (T) over untreated control (C) mice, revealed highly significant (p<0.001) tumor regression effects greater than standards. Life span of mice bearing advanced tumor for 10 days before the drug challenge was also considerably increased. Its toxicity was assessed in vivo in normal and S-180 bearing mice by measuring drug-induced changes in haematological parameters, femoral bone marrow and splenic cellularities as well as hepatotoxicity and nephrotoxicity sequentially on days 9, 15 and 21 following drug treatment at the optimum dose of 50 mg/kg from day 1 to 7. Results indicate that it did not adversely affect haematopoiesis. The other parameters were within normal limit. The compound comparable to standards inhibited the synthesis of DNA and RNA in S-1 80 tumor cells.
Samanta
Suva
S
Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Calcutta-700026, India.
Pain
Anindita
A
Dutta
Sushanta
S
Saxena
Ajit Kumar
AK
Shanmugavel
Mutiah
M
Pandita
Renu Moti
RM
Qazi
Gulam Nabi
GN
Sanyal
Utpal
U
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D007094:Imides / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use; D008130:Lomustine / Q000627:therapeutic use; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D053644:Naphthalimides; D009368:Neoplasm Transplantation; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012510:Sarcoma 180 / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007094:Imides; D007546:Isoquinolines; D009281:Naphthalenes; D053644:Naphthalimides; D012334:RNA, Neoplasm; C508512:nitronaphthal-NU; C019215:mitonafide; D008130:Lomustine; D004247:DNA; D013936:Thymidine; D014529:Uridine