Preparation and Biological Activity of Heteroaryl-Substituted Bile Steroids

Abstract

The synthesis, and growth inhibition studies against the L1210 mouse leukaemia, �MCF-7 human breast cancer and SKOV-3 ovarian carcinoma cell lines, of derivatives of lithocholic acid and cholic acid in which quinoline-3-carboxylate and acridine-9-carboxylate are substituted at the 3 and/or the 24 position are reported. The 3α,24-diheteroaryl-substituted steroid systems, lithocholic acid, cholic acid, quinoline and acridine-9-carboxylic acid showed no significant biological activity against any of the cell lines. In contrast, when either a single quinoline-3-carboxylate or acridine-9-carboxylate unit is substituted onto position 24 of the steroid derivatives, significant activity against L1210, and weak activity against the MCF-7 and SKOV-3 lines is exhibited. DNA thermal denaturation studies of these compounds showed no detectable binding to calf thymus DNA.