Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma associated herpesvirus

Tumors associated with Kaposi's sarcoma–associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. Latent viral proteins maintain the viral genome and are required for tumorigenesis. Current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can persist for the lifetime of the host. Thus, targeting latent viral proteins may prove to be an important therapeutic modality for existing tumors as well as in tumor prevention by reducing latent virus load. Here, we describe a novel fluorescence-based screening assay to monitor the maintenance of the Kaposi's sarcoma–associated herpesvirus genome in B lymphocyte cell lines and to identify compounds that induce its loss, resulting in tumor cell death

Myristicyclins A and B: Antimalarial Procyanidins from <i>Horsfieldia spicata</i> from Papua New Guinea

An antimalarial screen for plants collected from Papua New Guinea identified an extract of <i>Horsfieldia spicata</i> as having activity. Isolation of the active constituents led to the identification of two new compounds: myristicyclins A (<b>1</b>) and B (<b>2</b>). Both compounds are procyanidin-like congeners of myristinins lacking a pendant aromatic ring. Myristicyclin A was found to inhibit the ring, trophozoite, and schizont stages of <i>Plasmodium falciparum</i> at similar concentrations in the mid-μM range

Isolation of Pyrrolocins A–C: <i>cis</i>- and <i>trans</i>-Decalin Tetramic Acid Antibiotics from an Endophytic Fungal-Derived Pathway

Three new decalin-type tetramic acid analogues, pyrrolocins A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>), were defined as products of a metabolic pathway from a fern endophyte, NRRL 50135, from Papua New Guinea. NRRL 50135 initially produced <b>1</b> but ceased its production before chemical or biological evaluation could be completed. Upon transfer of the biosynthetic pathway to a model host, <b>1</b>–<b>3</b> were produced. All three compounds are structurally related to equisetin-type compounds, with <b>1</b> and <b>3</b> having a <i>trans</i>-decalin ring system, while <b>2</b> has a <i>cis</i>-fused decalin. All were active against <i>Mycobacterium tuberculosis</i>, with the <i>trans-</i>decalin analogues <b>1</b> and <b>3</b> exhibiting lower MICs than the <i>cis</i>-decalin analogue <b>2</b>. Here we report the isolation, structure elucidation, and antimycobacterial activities of <b>1</b>–<b>3</b> from the recombinant expression as well as the isolation of <b>1</b> from the wild-type fungus NRRL 50135