Novel Derivatives of Benfluron and Dimefluron: Synthesis and Anticancer activity

In this study, we tried to improve the anticancer properties of two potential cytostatic agents based on benzo[c]fluorene, benfluron and dimefluron, by the synthesis of their C-7 derivatives. In the new derivatives, we observed the effect in Ehrlich tumour-bearing mice as well as in human MCF-7, BT-549 and MDA-MB-231 cells. All of the compounds tested showed a strong inhibitory effect in vitro. When tested in vivo, their systemic toxicity in vivo was promisingly low. Benfluron and its O-methyloxime as well as dimefluron and its oxime, thiosemicarbazone and hydrazone inhibited tumour growth in vivo. Only benfluron and hydrazone of dimefluron prolonged the survival. Proliferating cell nuclear antigen (PCNA) protein was decreased in tumours treated with benfluron and O-methyloxime of dimefluron in cancer tissue. Benfluron thiosemicarbazone increased the infiltration of tumour with T-lymphocytes. Taken together, all derivatives were more cytotoxic then their parent compounds, but not necessarily more effective in vivo.