Highly Photoactive Psoralens with Low Mutagenicity

Despite extensive donor screening and improved tests for blood transfusion-associated diseasessuch as hepatitis and HIV remain significant problems. As a result, the development of an efficient andsafe process for the decontamination of blood components has become a goal o several research efforts.We have developed experimental protocols for a psoralen-based photochemical decontamination processfor platelet concentrates utilizing UVA light. The best candidate identified for viral inactivation was,however, also unacceptably mutagenic, as defined by the Ames assay. We have now discovered severalcompounds with significant anti-HIV activity under photodecontamination conditions that show lessmutagenicity. We seek to identify further compounds with enhanced activity and even lowermutagenicity for commercialization in the decontamination of platelet suspensions. This objective willbe achieved through the following specific aims: 1) synthesis of at least 20 new psoralens withpotential for improvement by both above criteria; 2) evaluation of the photoinactivating potential of thecompounds with a bacteriophage model. Successful compounds will be further tested in a photoinactiva-tion assay against HIV-1, as well; 3) evaluation of each compound in an Ames assay with both bacteriasensitive to frame shift mutagens and those sensitive to base substitution mutagens.