Helioxanthin

Helioxanthin (ACH126447) is a novel inhibitor of HBV, HCV and HSV-1 virus with EC50 values of 1 μM, 3 μM and 2 μM, respectively [1].

Helioxanthin has shown significant antiviral effect on HBV, HCV and HSV-1 virus in vitro with EC50 values of 1 μM, 3 μM and 2 μM, respectively. In a cell culture model, the level of HBV RNA, the expression of HBV antigen and its replication were all reduced by helioxanthin. Besides, helioxanthin has been exhibited to have a low cytotoxicity on both MT-223 and CEM24 cell lines with ID50 values of 2.5 μM and 31 μM, respectively [1].

Reference:
[1] Yeo H1, Li Y, Fu L, Zhu JL, Gullen EA, Dutschman GE, Lee Y, Chung R, Huang ES, Austin DJ, Cheng YC. Synthesis and antiviral activity of helioxanthin analogues. J Med Chem. 2005 Jan 27;48(2):534-46.

Helioxanthin suppresses the cross talk of COX-2/PGE2 and EGFR/ERK pathway to inhibit Arecoline-induced Oral Cancer Cell (T28) proliferation and blocks tumor growth in xenografted nude mice.[Pubmed:26464283]

Environ Toxicol. 2016 Dec;31(12):2045-2056.

Helioxanthin, an active compound from Taiwania cryptomerioides Hayata, has been shown to have various biological activities. However, their anticancer effect in oral squamous cell carcinoma has not been well established yet. Helioxanthin inhibited the proliferation of oral squamous cell carcinoma cells in a dose-dependent manner by inducing G2/M phase arrest. Similarly, Helioxanthin inhibited cyclooxygenase-2, (COX-2), phosphorylated EGFR, and extracellular-signal-regulated kinases (ERK) protein level and further reduced the nuclear accumulation of phosphorylated epidermal growth factor receptor (pEGFR) and activator protein-1(AP-1) family protein, c-fos. Moreover, Helioxanthin at the dose of 20 and 30 mg kg(-1) for 15 days reduced the tumor growth in animal model. This study demonstrated that Helioxanthin exerts its anticancer activity against oral cancer cells by downregulating EGFR/ERK/c-fos signaling pathway to inhibit COX-2 level and by activating cyclin-dependent kinase inhibitor (p27) to further induce G2/M cell cycle arrest. This Helioxanthin may serve as a novel candidate for oral cancer prevention. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2045-2056, 2016.

Helioxanthin analogue 8-1 inhibits duck hepatitis B virus replication in cell culture.[Pubmed:21107018]

Antivir Chem Chemother. 2010;21(2):97-103.

BACKGROUND: Current approved anti-HBV treatment cannot completely eliminate HBV infection, and emergence of resistant virus is an important treatment issue. Effective anti-HBV agents with different mechanisms of action on novel target sites are needed for the treatment of HBV infection and for combating the resistant virus, alone or in combination with current anti-HBV strategies. Helioxanthin analogue 8-1 displayed potent anti-HBV activity in human HBV in vitro and in animal models, with a unique antiviral mechanism. Its antiviral activity in other HBV system needs further study. METHODS: The anti-duck hepatitis B virus (DHBV) activity of 8-1, an analogue of a natural product, Helioxanthin, was studied in the DHBV inducible cell line, dstet5, in comparison to and in combination with the nucleoside analogue, lamivudine (3TC). RESULTS: Helioxanthin analogue 8-1 exhibited anti-DHBV activity as demonstrated by quantification of viral DNA, RNA, covalently closed circular DNA and protein synthesis. Analogue 8-1 did not affect the stability of cellular macromolecules and did not have a sustained antiviral effect after drug removal. When DHBV replication was induced, virus-harbouring cells were more susceptible to the cytotoxicity of 8-1 than non-induced cells. CONCLUSIONS: 8-1 exhibited effective inhibition on DHBV replication. The combination of 8-1 with 3TC resulted in additional anti-DHBV activity. Viral induced cells displayed higher susceptibility to 8-1 treatment than non-induced cells. HBV X protein might not be an essential factor in the initiation of the biological activity of 8-1, as demonstrated by its absence in DHBV. These findings warrant further development of 8-1 for the treatment of chronic hepatitis B and its associated diseases.

The Total Synthesis of Retrojusticidin B, Justicidin E, and Helioxanthin.[Pubmed:26047161]

J Org Chem. 2015 Jul 2;80(13):6708-14.

Making use of a tandem free radical cyclization process mediated by Mn(OAc)3 as a key operation, the total synthesis of retrojusticidin B, justicidin E, and Helioxanthin has been concisely achieved in four or five steps in an overall yield of 45, 33 and 44%, respectively, from a common starting material 5.

Synthesis and biological evaluation of helioxanthin analogues.[Pubmed:23465436]

Bioorg Med Chem. 2013 Apr 1;21(7):2163-76.

Helioxanthin and analogues have been demonstrated to suppress gene expression of human hepatitis B virus. In the continuous attempt to optimize antiviral activity, various structural motifs were grafted on the Helioxanthin scaffold. Many such analogues were synthesized and evaluated for their anti-hepatitis B virus activity. Structure-activity relationships of these Helioxanthin derivatives are also discussed. Among these new compounds, 15 exhibits the highest activity against HBV (EC50=0.06 muM). This compound can suppress viral surface antigen and DNA expression. Furthermore, viral RNA is also diminished while the core promoter is deactivated upon treatment by 15. A plausible working mechanism is postulated. Our results establish Helioxanthin lignans as potent anti-HBV agents with unique mode of action. Since their antiviral mechanism is distinct from current nucleoside/nucleotide drugs, Helioxanthin lignans constitute a potentially new class of anti-HBV agents for combination therapy.