In vitro studies on anthracycline haloderivatives.

A new class of anthracycline derivatives carrying a halogen atom in the 4' position of the aminosugar moiety was tested in cytotoxicity studies on HeLa cells and on P388 cell lines sensitive and resistant (P388/DX) to doxorubicin, in comparison with the parent drugs doxorubicin (DX) and daunorubicin (DNR). 4'-Haloderivatives of DX generally appear to be more cytotoxic than DX on HeLa, P388 and P388/DX cells. Cellular kinetic studies of DX-haloderivatives on HeLa, P388 and P388/DX cell lines show that they accumulate inside the cell in higher amounts than DX, whereas DNR haloderivatives accumulate in HeLa and P388 cells at levels similar to DNR; only in P388/DX is their accumulation higher as compared with DNR. The results reported suggest that, besides drug accumulation, other factors are involved in the cytotoxic mechanism of action of this class of compounds. Therefore 4'-haloderivatives represent a class of compounds with promising activity, in particular regarding anthracycline-resistant cell lines.