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Toxicity Studies of Triazolo-Thiadiazoles in Ehrlich Ascitic Carcinoma Cells

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Author Affiliations

  • 1Department of Chemistry, Manipal Institute of Technology, Manipal University, 576 104, INDIA
  • 2 Organic Chemistry Division, Department of Chemistry, National Institute of Technology, Surathkal, Mangalore 575 025, INDIA
  • 3 Department of Printing and Media Engineering, Manipal Institute of Technology, Manipal University, 576 104, INDIA
  • 4 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, 576 104, INDIA

Res. J. of Pharmaceutical Sci., Volume 2, Issue (6), Pages 1-6, August,30 (2013)

Abstract

Novel treatment approaches are urgently needed for cancer management due to high systemic toxicity and drug resistance in cancer chemotherapy. Three triazolo-thiadiazoles, 6-[3-(4-chlorophenyl)-1H-pyrazol-4-yl]-3-[(2-naphthoxy)methyl] [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazole (CPNT), 6-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-3-[(2-naphthoxy)methyl] [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazole (FPNT) and 6-[3-(4-chlororophenyl)-1H-pyrazol-4-yl]-3-[phenoxymethyl] [1,2,4] triazolo [3,4-b][1,3,4]thiadiazole (CPPT) were tested for their anti-tumor activity in ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. The effect of thiadiazoles in the mean survival time, body weight, hematological and biochemical parameters in cancer induced mice was studied. The inner peritoneal lining of mice was checked for angiogenesis. Histopathology studies of liver, kidney and spleen to assess the toxicity of thiadiazoles were performed. Statistical analyses were performed by one-way ANOVA, followed by Tukey’s post hoc test using Graph Pad Prism 5.02. An increase in mean survival time was observed in mice treated with CPNT, 50 mg/kg body weight over control and standard mice. The rise in body weight associated with progression of cancer was controlled on treatment with CPNT. Differed hematological and biochemical parameters in EAC bearing mice were restored towards normal after CPNT treatment. Histopathology studies exhibited only mild hepatic and nephrotoxicity on CPNT treatment. CPNT at an optimal dose of 50 mg/kg body weight inhibited angiogenesis and exhibited excellent anticancer activity with minimal toxic effects in vivo against EAC cells when compared to the standard drug cisplatin.

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