Evaluation of antitumor efficacy and toxicity of novel 6-nitro-2-(3-chloropropyl)-1H-benz[de]isoquinoline-1,3-dione in vivo in mouse.

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/Cmax values of 138 and 189 were obtained at its optimum dose of 60 mg/kg for QD1-7 . 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.