Novel disulfides with antitumor efficacy and specificity

Abstract

Some disulfides have previously been shown to possess antifungal and/or antileukaemic activity. Importantly, this cytotoxicity can be selective. We have previously shown that a subset of these compounds does not block the proliferative potential of normal, non-transformed cells. Based on these results and proposed mechanisms of action, a new set of structurally modified organosulfur compounds, including a-substituted disulfides and a thiosulfonate ester, have been prepared and evaluated for their potential as antileukaemic agents. Compounds were screened for antiproliferative activity against a panel of human cells derived from acute lymphocytic and acute myelogenous leukaemia, as well as non-transformed cells. We have identified five new disulfides and thiosulfonate that can trigger tumour cells to undergo cell death by an apoptotic mechanism in a sensitive and specific manner.