HEPATIC DIRECTED ANTIVIRAL AGENTS

THE OBJECT OF THIS RESEARCH IS TO DEVELOP AN ANTI-HEPATITIS B VIRUS PRO-DRUG WHICH WILL CONCENTRATE IN THE INFECTED LIVER TISSUE BY BINDING THE HEPATIC ASIALOGLYCOPROTEIN RECEPTOR AND RELEASING THE ACTIVE FORM OF THE DRUG IN THE HEPATOCYTE. TOWARD THIS END, A NUMBER OF ADENOSINE ARABINOFURANOSIDE/ARABINOGALACTAN CONJUGATES WILL BE SYNTHESIZED. THE CONJUGATES WILL BE EVALUATED AS SUITABLE PRODRUGS BY SEVERAL CRITICAL TESTS. INTERACTION WITH THE HEPATICASIALOGLYCOPROTEIN RECEPTOR IN VITRO WILL BE DETERMINED IN A COMPETITIVE BINDING ASSAY USING ISOLATED RAT HEPATOCYTES. THE RELEASE OF ADENOSINE ARABINOFURANOSIDE, OR IN SOME INSTANCES, ITS ALSO ACTIVE 5 MONOPHOSPHATE DERIVATIVE, WILL BE MEASURED IN VITRO ALSO USING A HEPATOCYTE CELL CULTURE A PRELIMINARY TOXICOLOGICAL EXAMINATION OF THE CONJUGATE CONSIDERED MOST SUITABLE AS A PRO-DRUG WILL BE CONDUCTED. THE RESEARCH IS EXPECTED TO LEAD TO AN ANTIVIRAL PRO-DRUG OF ADENOSINE ARABINOFURANOSIDE POSSESSING A GREATER POTENCY AND LOWERTOXICITY RELATIVE TO THE FREEDRUG.