Evaluation of Fluoren-NU as a Novel Antitumor Agent

Authors: Mukherjee, Asama; Dutta, Sushanta; Chashoo, Gousia; Bhagat, Madhulika; Saxena, Ajit Kumar; Sanyal, Utpal

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Volume 17, Number 9, September 2009 , pp. 387-396(10)

Publisher: Cognizant Communication Corporation

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Abstract:

A new nitrososourea derivative, namely fluoren-NU, 3-[2-{3-(2-chloroethyl)-3-nitrosouriedo}ethyl]spiro[5,9′-fluorenyl]imidazolidine-2,4-dione (compound 2e), was synthesized from 3-(2-bromoethyl)-spiro [5,9′-fluorenyl]imidazolidine-2,4-dione via a four-step synthetic procedure. Its chemical alkylating activity was assessed by coupling with 4-(4-nitrobenzyl)pyridine. In vitro screening in six human tumor cell lines, namely SK-N-SH CNS, IMR-32 neuroblastoma, A549 lung, DU-145 prostate, HL-60 leukemia, and U-937 lymphoma, revealed its significant cytotoxicity in SK-N-SH. Its in vivo antitumoral potency was assessed in murine ascites tumors Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice. Results revealed significant tumor regression effects in both of these tumors. Life span of mice bearing advanced tumor for 5 days before the drug challenge was also considerably increased. In vivo toxicological assay at its optimum dose of 40 mg/kg for days 1‐7 treatment schedule was conducted sequentially on day 9, 14, and 19 in normal and EAC-bearing mice. Results revealed that it did not adversely affect hematopoiesis or exhibit drug-induced hepatotoxicity and nephrotoxicity. It has shown minimal cytotoxic effect on human peripheral blood mononuclear cells (PBMC) having a high IC50 value of 792 M. Compared to Mitonafide and CCNU used as standards it also significantly inhibited DNA and RNA synthesis in EAC tumor cells in vitro at 8 M concentration.

Keywords: Antitumor agent; Cytotoxicity; In vivo assay; New nitrosourea; Toxicological assay; Tumor cells

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504009788912516

Publication date: September 1, 2009

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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