Four novel bis-(naphtho-γ-pyrones) isolated from Fusarium species as inhibitors of HIV-1 integrase

Integration of viral DNA into host cell DNA is an essential step in retroviral (HIV-1) replication and is catalyzed by HIV-1 integrase. HIV-1 integrase is a novel therapeutic target and is the focus of efforts to identify effective inhibitors that will prevent, or cure HIV infections, Four novel naphtho-gamma-pyrones belonging to the chaetochromin and ustilaginoidin family, were discovered as inhibitors of HIV-1 integrase from the screening Of fungal extracts using a recombinant in vitro assay. These compounds inhibit both the Coupled and strand transfer activity of HIV-1 integrase with IC50 values of 1-3 and 4-12 muM respectively. The discovery structure elucidation chemical modification and the structure-activity relationship of these compounds are described. (C) 2003 Elsevier Science Ltd. All rights reserved.