Cryptofolione
Z-Cryptofolione and Cryptomoscatone D2 as highly efficacious inhibitors of the G(2) checkpoint, G(2) checkpoint inhibitors can force cells arrested in G(2) phase by DNA damage to enter mitosis. Cryptofolione shows moderate cytotoxicity in both macrophages and T. cruzi amastigotes, it also displays a mild inhibitory effect on the promastigote form of Leishmania spp.
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Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to
24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
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The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.
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J Pharm Pharmacol. 2001 Apr;53(4):563-7.
Cryptofolione derivatives from Cryptocarya alba fruits.[Pubmed:
11341375]
METHODS AND RESULTS:
Cryptofolione (1) and the new Cryptofolione derivative 6-(4,6-dimethoxy-8-phenyl-octa-1,7-dienyl)-4-hydroxy-tetrahydro-pyran-2-one (2) were isolated from the fruits of Cryptocarya alba. The structures were elucidated by spectroscopic methods. Cryptofolione showed activity towards Trypanosoma cruzi trypomastigotes, reducing their number by 77% at 250 microg mL(-1).
CONCLUSIONS:
Cryptofolione showed moderate cytotoxicity in both macrophages and T. cruzi amastigotes. It also displayed a mild inhibitory effect on the promastigote form of Leishmania spp.
As both cytotoxic and trypanocidal effects are similar, the compound presented little selectivity in our assay models.
Cancer Chemother Pharmacol. 2008 Mar;61(3):407-13.
Abrogation of ionizing radiation-induced G2 checkpoint and inhibition of nuclear export by Cryptocarya pyrones.[Pubmed:
17440726 ]
METHODS AND RESULTS:
G(2) checkpoint inhibitors can force cells arrested in G(2) phase by DNA damage to enter mitosis. In this manner, several G(2) checkpoint inhibitors can enhance killing of cancer cells by ionizing radiation and DNA-damaging chemotherapeutic agents, particularly in cells lacking p53 function. All G(2) checkpoint inhibitors identified to date target protein phosphorylation by inhibiting checkpoint kinases or phosphatases. Using a phenotypic cell-based assay for G(2) checkpoint inhibitors, we have screened a large collection of plant extracts and identified Z-Cryptofolione and Cryptomoscatone D2 as highly efficacious inhibitors of the G(2) checkpoint. These compounds and related pyrones also inhibit nuclear export. Leptomycin B, a potent inhibitor of Crm1-mediated nuclear export, is also a very potent G(2) checkpoint inhibitor.
CONCLUSIONS:
These compounds possess a reactive Michael acceptor site and do not appear promising as a radiosensitizing agents because they are toxic to unirradiated cells at checkpoint inhibitory concentrations.
Nevertheless, the results show that inhibition of nuclear export is an alternative to checkpoint kinase inhibition for abrogating the G(2) checkpoint and they should stimulate the search for less toxic nuclear export inhibitors.
