O-Methylviridicatin is a natural derivative of the alkaloid mycotoxin viridicatin produced by several species of Penicillium. The scaffold of quinolin-2(1H)-one is a useful structural motif found in many natural products. In particular, derivatives of 4-arylquinolinones have attracted attention for their anticancer/antiviral activities. O-Methylviridicatin is a fungal metabolite that can inhibit the tumor necrosis factor alpha (TNFα)-induced replication of HIV.
O-Methylviridicatin is soluble in ethanol, methanol, DMSO and DMF but is practically insoluble in water.
| Microbiology Applications | During a high-throughput, cell-based, virus-free assay screening system, 15,000 fungal extracts were screened and the metabolite 3-O-Methylviridicatin was shown to be an inhibitor of cytokine tumour necrosis factor alpha (TNFα)-induced replication of HIV. This factor activates transcription of the provirus in both T-cells and macrophages. It blocked TNF- α activation of the HIV long terminal repeat (LTR) in a HeLa-based system (IC50 =5 µM), and inhibited HIV replication in OM-10.1 cell line, which are HL-60 promyelocytes infected with HIV-1, which is a model of TNF-α-induced chronic infection (IC50 =2.5µM)(Heguy et al, 1998).
The synthesis of O-Methylviridicatin and its several analogs have shed insights into the development of new anti-inflammatory agents. In particular, 4-phenyl-3-methylthioquinolinone had an enhanced ability to inhibit TNF-α-secretion (Sun et al, 2015). |
| References | Bracken A, Pocker A and Raistrick H (1954) Studies in the biochemistry of microorganisms. 93. Cyclopenin, a nitrogen-containing metabolic product of Penicillium cyclopium Westling. Biochem J. 57(4):587-595 PMID 13198807 Ciegler A and Hou CT (1970) Isolation of viridicatin from Penicillium palitans. Arch. Mikrobiol. 73(3):261-267 PMID 5487865 Heguy A et al (1998) Isolation and characterization of the fungal metabolite 3-O-methylviridicatin as an inhibitor of tumor necrosis factor alpha-induced human immunodeficiency virus replication. Antivir. Chem. Chemother. 9(2):149-155 PMID 9875386 Ma YM et al (2017) A new isoquinolone alkaloid from an endophytic fungus R22 Nerium indicum. Nat. Prod. Res. 31(8):951-958 PMID 27910702 Ribiero N et al (2007) Synthesis of 3-O-methylviridicatin analogues with improved anti-TNF-a properties. Bioorg. & Med. Chem. Lett. 17(20):5523-5524 Sun B et al (2015) A novel and facile synthesis of 4-arylquinolin-2(1H)-ones under metal-free conditions. Chin. Chem. Lett. 26:977-979 |
