DERIVATIVES OF A NOVEL CYCLOPEPTOLIDE .2. SYNTHESIS, ACTIVITY AGAINSTMULTIDRUG-RESISTANCE IN CHO AND KB CELLS IN-VITRO, AND STRUCTURE-ACTIVITY-RELATIONSHIPS

A series of derivatives of the novel cyclopeptolide 1 was prepared, an d their ability to chemosensitize multi drug resistant CHO and KB cell s in vitro was evaluated. In contrast to the parent compound, several of the derivatives were found to be highly active. In particular, conv ersion of the R-lactic acid residue of 1 into its S-isomer via lactone ring cleavage and recyclization with inversion resulted in a marked e nhancement of activity. Some of these derivatives (e.g., 15a, SDZ 280. 446) belong to the most potent resistance modulating compounds known s o far.