Isolation and Characterization of the Fungal Metabolite 3-O-Methylviridicatin as an Inhibitor of Tumour Necrosis Factor α-Induced Human Immunodeficiency Virus Replication

Abstract

The cytokine tumour necrosis factor α (TNF-α) has been shown to play a role in human immunodeficiency virus (HIV) replication by activating transcription of the provirus in both T cells and macrophages. Therefore, agents that block TNF-α-induced HIV expression could have therapeutic value in the treatment of AIDS. We have sought to identify antiviral agents that block TNF-α induction of HIV LTR-directed transcription, using a cell-based, virus-free assay system in automated high-throughput screening. HeLa cells were transfected with an HIV LTR-luciferase reporter plasmid and a stable line was isolated in which TNF-α increased luciferase production by two-to threefold. This cell line was used to screen approx-

Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines

“…6 Cyclopenin, the only naturally produced 1,4-benzodiazepine-2,5-one isolated, is particularly interesting as the biosynthetic intermediate of viridicatin, 7 an inhibitor of replication of HIV. 8 The naturally produced TLN-4601 (formerly ECO-4601) is the sole member of the dibenzodiazepinones' group, 9 with a broad spectrum of antitumor activity in cancer cells and human xenografts. 10 Phase I/II trials (Thallion Pharma company web site: http:// www.thallion.com/en/drug-development/tln-4601.php) are underway.…”

A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium polonicum AP2T1

“…Quinolinones, including many 2-quinolinones, are known for their structural diversity and broad bioactivity spectrum covering cytotoxic (Venet et al 2003;Wei et al 2011 (Cunningham & Freeman 1953), antiviral (Heguy et al 1998), herbicidal (Salmon et al 2010), antidepression activities (Obrenovitch & Zilkha 1996) and so on. As a promising resource, marine fungi can produced quite diverse bioactive compounds including 2-quinolinones (Bugni & Ireland 2004;He et al 2005;Wei et al 2011).…”

Mechanistic Elucidation of Two Catalytically Versatile Iron(II)- and α-Ketoglutarate-Dependent Enzymes: Cases Beyond Hydroxylation

“…Viridicatin-type alkaloids consist of a subfamily of naturally abundant quinolone alkaloids. They have been isolated from both terrestrial and marine fungi of the genera Aspergillus and Penicillium [119][120][121][122][123], and exhibit pharmaceutically valuable biological activities, including antiviral (including anti-HIV), antibacterial, and antitumor activities [124][125][126][127][128][129][130][131]. Recently, a gene cluster from Aspergillus nidulans responsible for the biosynthesis of the viridicatin has been discovered [ 132 ].…”