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