RECENT PROGRESS AND PROSPECTS ON PLANT-DERIVED ANTI-HIV AGENTS AND ANALOGS - Medicinal Chemistry of Bioactive Natural Products - page 357

RECENT PROGRESS AND PROSPECTS
ON PLANT-DERIVED ANTI-HIV
AGENTS AND ANALOGS

D ONGLEI Y U AND K UO -H SIUNG L EE
Natural Products Laboratory, School of Pharmacy, University of North Carolina,
Chapel Hill, NC

9.1 INTRODUCTION

Acquired immunodeficiency syndrome (AIDS), a degenerative disease of the
immune system, is caused by the human immunodeficiency virus (HIV) and results
in life-threatening opportunistic infections and malignancies. 1-3 As the world enters
the third decade of the AIDS epidemic, this pandemic has spread rapidly through
the human population and become the fourth leading cause of mortality world-
wide. 4 The rapid spread of AIDS prompted an extensive search for chemotherapeu-
tic anti-HIV agents. Large numbers of naturally and synthetically derived chemical
entities were screened for potential anti-HIV activity. As a result, numerous com-
pounds were found to have anti-HIV activity. Since then, 20 anti-HIV drugs have
been approved by the U.S. Food and Drug Administration (FDA), including reverse
transcriptase inhibitors (RTIs), protease inhibitors (PIs), and a fusion inhibitor. 5
Emergence of drug-resistant viruses and the side effects and toxicity of these agents
have limited their benefits in AIDS treatment. 6-10 Therefore, the current develop-
ment of new, effective, and less toxic anti-HIV agents is focusing on novel struc-
tures or new modes of action.
Figure 9-1 describes the modern drug research process. Our drug discovery pro-
gram focuses on new lead discovery and lead optimization, using natural products
as a reservoir of biologically active compounds. Many efforts have attempted to