The design, synthesis, and preliminary evaluation of novel antiviral photosensitizers for the purification of selected blood products.

摘要

With the continual onslaught of new viruses entering into the human population such as the increasing list of hepatitis viruses, the need for a completely safe supply of blood products is definitely a major interest among the health care industry. Presently, the blood supply is screened for the presence of the following infectious agents: human immunodeficiency viruses, types 1 and 2; hepatitis viruses, B and C and human T-cell lymphotropic viruses, types 1 and 2. Although the risk of contracting one of these viruses during transfusion is small, infection would result in serious ramifications that could prove life threatening.; Coumarins and psoralen derivatives were chosen to be the photosensitizers in this work because salubrious effects had been associated with both types of compounds for many years. These molecules were designed to inactivate viruses, bacteria or parasites by damaging their nucleic acids. Nucleic acids were chosen as the target for inactivation because whole blood and blood products are devoid of nuclei that contain the genomic nucleic acids. Another reason for deciding upon these two classes of compounds was that they were planar aromatic molecules. Planar aromatic compounds were known to intercalate between the base pairs of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If either molecule could penetrate into the DNA/RNA of the virus, bacterium or parasite, a nucleic acid break could occur upon irradiation with ultraviolet light that should result in the inactivation of the virus or bacteria.; T-4 bacteriophage was used in preliminary tests to determine the activity of the photosensitizers synthesized. T-4 phage was a useful model for comparative studies for viruses that are devoid of a lipid bilayer and are difficult to inactivate such as parvovirus B19 and hepatitis A. Two derivatives: 3-Bromo-7-(3-aminopropoxy)-4,8-dimethylcoumarin hydrochloride and 3-Bromo-4,8-dimethyl-7-(3-morpholinopropoxy)coumarin were capable of causing a 3.4 and a 4.6 viral log{dollar}sb {lcub}10{rcub}{dollar} reduction respectively in the absence of oxygen at concentrations of about 2 {dollar}mu{dollar}g/ml.