Vol. 185, No. 1, 1992 May 29, 1992 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 370-378 HIV-1 AND HIV-2 REVERSE TRANSCRIPTASES: A COMPARATIVE STUDY OF SENSITIVITY TO INHIBITION BY SELECTED NATURAL PRODUCTS GHEE T. TAN 1, JAMES F. MILLER +, A. DOUGLAS KINGHORN 1, STEPHEN H. HUGHES 2 and JOHN M. PEZZUTO 1'3. 1program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 2NCI - Frederick Cancer Research and Development Center, ABL - Basic Research Program, Frederick, Maryland 3Specialized Cancer Center, University of Illinois College of Medicine at Chicago, Chicago, Illinois 60612 Received April 13, 1992 SUMMARY: One hundred and fifty six pure natural products, which had previously been tested against HIV-1 reverse transcriptase, were evaluated for HIV-2 reverse transcriptase inhibitory activity. Compounds that lacked effect in the HIV-1 reverse transcriptase system were found also to be inactive against HIV-2 reverse transcriptase. However, compounds belonging to the benzophenanthridine and protoberberine classes of alkaloids, certain flavonoids, the iridoid, fulvoplumierin, and the ansamycin antibiotic, daunomycin, exhibited similar potencies in both enzyme systems. In contrast, HIV-2 reverse transcriptase was observed to be four-fold more sensitive toward the inhibitory effects of the ipecac alkaloids, O-methylpsychotrine sulfate heptahydrate and psychotrine dihydrogen oxalate. Such differences in susceptibilities to inhibitors may indicate subtle dissimilarities in enzyme structure and function. ®~992~o~d~o Press, =no. Human immunodeficiency virus type 1 (HIV-1) is responsible for the current pandemic of acquired immunodeficiency syndrome (AIDS) (1). A second immunodeficiency virus (designated HIV-2), which is found predominantly in West Africa, was subsequently isolated from patients with AIDS and AIDS-related complex (2). The genome of HIV-2 has +Present address : Department of Chemistry, Whitney Young High School, Chicago, Illinois 60607. *To whom correspondence should be addressed. ABBREVIATIONS: RT, reverse transcriptase; MP, O-methylpsychotrine sulfate heptahydrate; PDO, psychotrine dihydrogen oxalate. 0006-291X/92 $4.00 Copyright © 1992 by Academic Press, Inc. All rights of reproduction in any form reserved. 370