Evaluation of antitumor efficacy and toxicity of novel 6-nitro-2-(3-chloropropyl)-1H-benz[de]isoquinoline-1,3-dione in vivo in mouse
| Autor: | Asama Mukherjee, Sushanta Dutta, Utpal Sanyal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Drug Evaluation Preclinical Antineoplastic Agents Pharmacology Kidney naphthalimide based compound lcsh:RC254-282 Ehrlich ascites carcinoma Nephrotoxicity Mice Bone Marrow In vivo Cell Line Tumor Blood plasma Animals Humans Potency Medicine Radiology Nuclear Medicine and imaging plasma stability Cardiotoxicity business.industry toxicity General Medicine Isoquinolines lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Xenograft Model Antitumor Assays In vivo assay medicine.anatomical_structure Liver Oncology Toxicity novel antitumor agent Bone marrow business Spleen |
| Zdroj: | Journal of Cancer Research and Therapeutics, Vol 9, Iss 3, Pp 442-446 (2013) |
| ISSN: | 1998-4138 0973-1482 |
| Popis: | Aim: This study was aimed to assess the in vivo anti-tumoral potency of the novel 6-nitro-2-(3-chloropropyl)-1H-benz[de]isoquinoline-1,3-dione [Compound 1] that has earlier demonstrated excellent cytotoxicity in 15 out of 17 human tumor cell lines tested. Materials and Methods: Two murine tumors namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) were used to measure its in vivo anti-tumor activity through the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Drug-induced toxicity in respect of hematological parameters, femoral bone marrow and splenic cellularity as well as biochemical parameters and histopathology of liver and kidney were assessed in vivo in normal and S-180 bearing mice sequentially on days 9, 14 and 19 following drug treatment at the optimum dose of 60 mg/kg administered from day 1 to 7. Results: Results revealed significant tumor regression effects in S-180 and EAC as T/C max values of 138 and 189 were obtained at its optimum dose of 60 mg/kg for QD 1-7 . Toxicity assay indicated no significant cardiotoxicity, hepatotoxicity or nephrotoxicity of the compound in normal and S-180 bearing mice. An initial hyposplenic cellularity and the femoral bone marrow suppression effect observed on day 9 reached normalcy by day 19. HPLC analysis revealed that it has appreciable stability (half-life ~ 3 h) in murine blood plasma in vitro. Conclusion: Above results justify potential candidature of the compound for further drug development. |
| Databáze: | OpenAIRE |
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