Effect of a new 1,3,4-thiadiazolium mesoionic compound (MI-D) on B16-F10 murine melanoma.
The structural characteristics of mesoionic compounds, which contain distinct regions of positive and negative charges associated with a poly-heteroatomic system, enable them to cross cellular membranes and interact strongly with biomolecules. Potential biological applications have been described for mesoionic compounds. In this study we evaluated the antitumour activity of 4-phenyl-5-(4-nitrocinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride (MI-D), a new mesoionic compound, against the mouse melanoma B16-F10 cell line. In vitro assays showed that MI-D interferes with both cell viability and proliferation. MI-D was cytotoxic to B16-F10 cells; cell viability, which was determined at various time intervals (1-72 h) and in the presence of different concentrations of the drug (2.5-75 micro M), was reduced by approximately 80% following 24 h exposure at 25 micro M. The proliferation rate evaluated over 72 h using varying subcytotoxic and cytotoxic concentrations (2.5-25 micro M) decreased in a dose-dependent manner. The in vivo antitumour activity of the drug was evaluated using a subcutaneous B16-F10 melanoma tumour in C57BL/6 mice. Animals were given MI-D intraperitoneally at a single dose of 57 micro mol/kg, 24 h after cell inoculation. Positive controls were treated with fotemustine and dacarbazine, which have known effects on melanoma cells. On day 17, tumours were excised and their weights were determined. MI-D inhibited tumour growth by 85%. This is a very encouraging result with regard to the possibility of MI-D becoming a new tool for melanoma research and treatment.
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D002934:Cinnamates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D013830:Thiadiazoles; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
C116348:4-phenyl-5-(4-nitrocinnamoyl)-1,3,4-thiadiazolium-2-phenylamine; D002934:Cinnamates; D013830:Thiadiazoles; D013844:Thiazoles