Antitumor activity of Nitronaphthal-NU, a novel mixed – function agent
Suva Samanta, Anindita Pain, Sushanta Dutta, Ajit Kumar Saxena, Mutiah Shanmugavel, Renu Moti Pandita, Gulam Nabi Qazi and Uptal Sanyal
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-180 tumor cells.