engleski

Effects of 4, 9-diazapyrenium derivatives on mouse tumor cells in vitro and in vivo

The 4, 9-diazapyrenium derivatives: 4-methyl-2, 7-diamino-5, 10-diphenyl-4, 9-diazapyrenium hydrogensulfate (ADAP) and 4, 9-dimethyl-4, 9-diazapyrenium hydrogensulfate (GDAP) are newly synthesized DNA intercalators. ADAP is additionaly an RNA intercalator, unlike GDAP. Antiproliferative activity of 4, 9-diazapyrenium derivatives was analysed in vitro on two mouse tumor cell lines, fibrosarcoma (FsaR) and squamous carcinoma (SCCVII), using the MTT assay. Toxicity and antitumor activity of ADAP and GDAP in vivo were investigated on C3Hf/BuZGr mice strain. ADAP caused strong growth inhibitory effect on both mouse tumor cell lines in concentration 1-100 μ M, in comparison to GDAP which caused statistically significant difference from control on FsaR in concentrations 10 μ M and 100 μ M, and on SCCVII in concentration 100 μ M. Histopathological analysis of microscopic slides of the organs of mice treated with single and multiple applications of 4, 9-diazapyrenium derivatives in concentration 25 mg/kg showed that there were no morphological changes of tissues and organs (liver, kidney, lung, spleen, heart, testicle, stomach, brain, bone, small intestine, colon, eye). Given results were confirmed by hematological and clinical-chemical analysis of blood of treated animals. Tumor growth of melanoma (B16-F10) and fibrosarcoma (FsaR) cells implanted in mice were not significantly reduced by single and multiple applications of 25 mg/kg of ADAP and GDAP.

4; 9-diazapyrenium derivatives; cytotoxicity; toxicity in vivo; antiproliferative activity in vivo

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