Estimation of the lipophilicity of new anticancer and immunosuppressive 1,8-diazaphenothiazine derivatives.

The lipophilicity of anticancer and immunosuppressant active 1,8-diazaphenothiazine derivatives ( 1: - 16: ) has been investigated. Their lipophilicity (RM0 and log PTLC) was determined by reversed-phase thin-layer chromatography with mixtures of acetone and TRIS buffer as mobile phases. The parameter RM0 and specific hydrophobic surface area b were significantly intercorrelated showing congeneric classes of dipyridothiazines. The parameter RM0 was discussed in the terms of the structure-lipophilicity relationships and transformed into parameter log PTLC by use of the calibration curve. The lipophilicity was correlated with molecular and biomolecular descriptors (human intestinal absorption, blood-brain barrier, plasma protein binding, MDCK) and in vitro tumor necrosis factor alpha inhibition and antiproliferative activity.