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| Names | |
|---|---|
| Preferred IUPAC name 3-Hydroxy-2-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-5-pentylcyclohexa-2,5-diene-1,4-dione | |
| Identifiers | |
3D model (JSmol) | |
| ChemSpider |
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| UNII | |
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| Properties | |
| C21H28O3 | |
| Molar mass | 328.445 g/mol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
HU-331 is aquinoneanticarcinogenic drug synthesized fromcannabidiol, acannabinoid in theCannabis sativa plant. It showed a great efficacy againstoncogenic human cells. HU-331 does not cause arrest incell cycle,cell apoptosis orcaspase activation. HU-331 inhibits DNAtopoisomerase II even at nanomolar concentrations, but has shown a negligible effect on the action of DNAtopoisomerase I. The cannabinoid quinone HU-331 is a very specificinhibitor of topoisomerase II, compared with most knownanticancer quinones.[1] One of the main objectives of these studies is the development of a newquinone derived compound that produces anti-neoplastic activity while maintaining low toxicity at therapeutic doses.
Inhibitors oftopoisomerases can act at two different levels. First inhibiting topoisomerase, which stabilize the topoisomerase-DNA complex and thus introduce DNA breaks in the wires that lead toapoptosis, then inhibiting the catalytic activity of topoisomerase, which hinders the activity of these enzymes without introducing breaks into the DNA chains. HU-331 seems to be acatalytic inhibitor of topoisomerase II, probably byenzymatic ligation to the protein. This molecule does not cause damage to DNA, but protects cells from damage, natural, or induced by other inhibitors of topoisomerase II that act as inhibitors of topoisomerase. Even when 60% of the target cells are killed by treatment with HU-331, other cells' nucleic content remains unharmed, with less breakage of DNA chains that control important cellular functions.[2]
Doxorubicin, like other anticancer quinones, was used forchemotherapy in human cancers for many years. The mechanism of action of these drugs has been the subject of considerable controversy sincechemotherapeutic drugs exert theircytotoxic effect on target cells by nonspecific mechanisms. The doxorubicin damages DNA byintercalation, the generation ofreactive oxygen species and inhibition of DNA topoisomerase I and II. This leads to breaking the chains of DNA single and double strands. The protein associated with these ruptures are the topoisomerase II and DNA damage is catalyzed by this enzyme.[2] Thus, while doxorubicin and otheranthraquinones act through many mechanisms such as apoptosis,abrogation of the cell cycle cell, activation of caspases, generation ofROS, inhibition of both topoisomerases, activation ofintracellularsecondary messengers, etc. Hu-331 is more active and less toxic, since it generates reactive oxygen species in theheart and has a specific activity that gives great potential to develop as a new anticancer drug, according to Koganet al.[2]
Cannabinoids can act as anticancer compounds killing severaloncogenic cells followed by direct interaction with cannabinoid receptors. The growth ofglioma is inhibited by a selective activation of theCB2 cannabinoid receptor andendogenous cannabinoids such asanandamide inhibit theproliferation of cells involved inlung cancer. The reason behind the antitumor effect of HU-331 appears unknown ascannabinoid receptor antagonists do not inhibit HU-331, despite being mediated by a cannabinoid receptor. The HU-331 exerts anantiangiogenic effect accompanied by apoptosis ofendothelial cells. Although in some studies. HU-331 has not caused the death of cells by oncogenic apoptosis. The conclusion that would lead cells to apoptosis based on treatment with the drug did not increase the proportion of cells containingDNALues in the sub-G1 phase and have not found the expression ofcaspase-3 in cancer cells.[2]
HU-331 is not scheduled at the federal level in theUnited States.[3]
"HU-331 (3-hydroxy-2-[(1R,6R)-3-methyl-6-(1- methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-2,5-cyclohexadiene-1,4-dione)" is a Schedule Icontrolled substance in the state ofFlorida making it illegal to buy, sell, or possess in Florida.[4]
"3-hydroxy-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-2,5-cyclohexadiene-1,4-dione, commonly known as HU-331" is a Schedule I controlled substance in the state ofWisconsin making it illegal to buy, sell, or possess in Wisconsin.[5]
HU-331 is included on the list of novel psychoactive substances (55/2014. [XII. 30.] EMMI rendelet) in Hungary.[6]
