Antiproliferative Effect of Novel XXXX -based Compounds.

@entity291 @entity16776 @entity5257 @entity5 @entity98 @entity35 @entity121
UNASSIGNED: We tested the antiproliferative activity and mechanism of the action of several novel @entity16776 derivatives. Six different @entity5 cell lines were used to evaluate the potential cytotoxic effect of eleven @entity16776 -based molecules. A standard @entity98 assay was used for cell bioavailability analysis. Additionally, the potential cytotoxic effect of the tested compounds on non- @entity5 cells was investigated in @entity35 skeletal @entity121 (L6) and in @entity291 aortic smooth muscle cells. In order to investigate whether the DNA binding activity of tested compounds correlated with their cytotoxic effect, circular dichroism (CD) measurement and DNA T4 ligase assay were performed. Finally, the potential mutagenic activity of the lead compound 5 was investigated. The cytotoxic effect of compound 5 in @entity5 cells was obtained in lower concentrations than the well-known: @entity16776 based drug, @entity5257 . The lead compound binds to DNA, but in a different mode than the parent molecules. Additionally, compound 5 was not cytotoxic in the effective range of concentrations in non- @entity5 cells. In identical concentrations, the parent compound ( @entity16776 ) and @entity5257 were extremely toxic for both types of these normal cells. Finally, based on CD measurement and T4 ligase assay, it was confirmed that 5 binds to DNA but in different from the parent compounds manner. Important to mention, that compound 5 might have increased mutagenic activity which must be verified in vivo. Based on these in vitro results, we conclude that 5 is a more potent and more selective antiprolifirative compound than @entity5257 . Compound 5 was also more effective in HepG2 and P-12 cells. Thus, 5 is suitable for future in vivo biological evaluation and its structure might be used as a basis for developing novel anticancer drugs.
