Design and Synthesis of Pironetin Analogue/Combretastatin A-4 Hybrids and Evaluation of Their Cytotoxic Activity

We describe the preparation of a series of hybrid molecules containing a combretastatin A-4 moiety and a pironetin analogue fragment linked by an ester spacer of variable length. The cytotoxic activities of these compounds have been measured and the relationship between the structure and cytotoxicity is discussed. Some of the tested compounds showed cytotoxicity values of the same order of magnitude as those of the parental molecules, combretastatin A-4 and pironetin, and were less toxic than the latter for normal cells.