NITROBENZYL-BASED PHOTOSENSITIVE PHOSPHORAMIDE MUSTARDS - SYNTHESIS AND PHOTOCHEMICAL PROPERTIES OF POTENTIAL PRODRUGS FOR CANCER-THERAPY

Several nitrobenzyl-based photosensitive phosphoramide mustards were s ynthesized. The nitrobenzyl moiety was structurally varied to find the most promising prodrug candidates in respect to photorelease and acti vity of the alkylating species. The synthesis of these compounds prove d to be applicable even in regard to compounds with additional functio nalization. The target molecules 13a,b to 14 exhibited the expected re d shift in their absorption spectra maximum compared to the parent nit robenzyl moiety. As seen by UV and P-31 NMR spectroscopy the phosphora mide mustard was quickly liberated upon irradiation with mercury are l amps. Assaying the structurally different prodrugs on their alkylating activity showed that compounds 13b and 14, derived from secondary ben zyl alcohols, are promising prodrug candidates. Their water solubility and the possibility of attaching macromolecules are encouraging vis-g -vis future investigations on their in vitro cytotoxicity.