Accession Number : ADA239210


Title :   Suicide Inhibitors of Reverse Transcriptase in the Therapy of AIDS and Other Retroviruses


Descriptive Note : Annual rept. 1 Jul 1988-30 Jun 1989


Corporate Author : GEORGE WASHINGTON UNIV WASHINGTON DC


Personal Author(s) : Bailey, Martyn J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a239210.pdf


Report Date : 01 Jul 1989


Pagination or Media Count : 22


Abstract : This project is concerned with the synthesis of suicide inhibitors of reverse transcriptase. This is a key enzyme in replication of HIV, the causative agent of AIDS. A suicide substrate contains a latent reactive group which becomes activated only as a consequence of the normal catalytic activity of the target enzyme and irreversibly inactivates it. Suicide substrates are thus inherently selective and have less side effects when used as drugs. We have synthesized over 40 compounds with these potentialities and screened them for antiviral activity in tissue culture. A number of active compounds, including a new class, the nucleoside spiroxiranes, have been identified which inhibit viral replication in cell culture. These compounds do not inhibit normal cell growth as shown by their favorable therapeutic index on lymphocyte cytotoxicity assays and because of their novel properties, show considerable promise as a new generation of antivirals.


Descriptors :   *ANTIVIRAL AGENTS , *HUMAN IMMUNODEFICIENCY VIRUSES , *ENZYME INHIBITORS , ENZYMES , REACTIVITIES , THERAPY , CATALYSTS , CYTOTOXINS , PATHOLOGY , DRUGS , CELLS(BIOLOGY) , CULTURES(BIOLOGY) , LYMPHOCYTES , BIOSYNTHESIS , ACQUIRED IMMUNE DEFICIENCY SYNDROME , BIOASSAY , TISSUE CULTURE , RETROVIRUSES , DORMANCY , NUCLEOSIDES , VIROLOGY


Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE