- Honokiol
Chembox new
Name = Honokiol
ImageFile = honokiol.png
IUPACName = 2-(4-hydroxy-3-prop-2-enyl-phenyl)- 4-prop-2-enyl-phenol
OtherNames = houpa, hnk
Section1 = Chembox Identifiers
SMILES = C=CCC1=CC(=C(C=C1)O)C2=CC (=C(C=C2)O)CC=C
CASNo = 35354-74-6
Section2 = Chembox Properties
Formula = C18H18O2
MolarMass = 266.334 g/mol
Appearance = White solid
Solubility = sparingly (25 °C)
Section8 = Chembox Other
Function =biphenols
OtherFunctn =diethylstilbestrol ,dihydroxyeugenol ,resorcinol
OtherCpds =magnolol Honokiol (C18H18O2) is a biphenolic compound present in the cones, bark, and leaves of "
Magnolia grandifloris" that has been used in the traditional Japanese medicine "Saiboku-to" as ananxiolytic ,anti-thrombotic ,anti-depressant ,anti-emetic , andanti-bacterial . While early research on the effective compounds in traditional remedies have simply used whole magnolia bark extracts, known ashoupu magnolia , recent work has identified honokiol and its structuralisomer magnolol as the active compounds in magnolia bark. In the late 1990's, honokiol saw a revival in western countries as a potent and highly tolerableanti-tumorigenic andneurotrophic compound.Biological Activity
"Anti-tumorigenic activities"
Honokiol has shown pro-apoptotic effects inmelanoma ,sarcoma ,myeloma ,leukemia , bladder,lung ,prostate , andcolon cancer cell lines1-4. Honokiol inhibits phosphorylation ofAkt , p44/42mitogen-activated protein kinase (MAPK), andsrc . Additionally, honokiol modulates thenuclear factor kappa beta (NfKB) activation pathway, an upstream effector ofvascular endothelial growth factor (VEGF),cyclooxygenase 2 (COX-2), andMCL1 , all significant pro-angiogenic and survival factors. Honokiol induces caspase-dependentapoptosis in a TRAIL-mediated manner, and potentiates the pro-apoptotic effects ofdoxorubicin and otheretoposides . So potent is honokiol's pro-apoptotic effects that it overcomes even notoriously drug resistant neoplasms such as multiple myeloma and chronicB-cell leukemia ."Neurotrophic Activity"
Honokiol has been shown to promoteneurite outgrowth and haveneuroprotective effects inrat corticalneurons . Additionally, honokiol increases free cytoplasmic Ca2+ in rat cortical neurons5."Anti-thrombolytic"
Honokiol inhibits platelet aggregation in rabbits in a dose-dependent manner, and protects cultured RAEC against oxidized low densityliproptein injury. Honokiol significantly increases theprostacyclin metabolite6-keto-PGF1alpha , potentially the key factor in honokiol's anti-thrombotic activity6.Purification
Several methods for purifying honokiol have been utilized. As honokiol exists naturally with its structural isomer
magnolol , which differs from honokiol only by the position of onehydroxyl group , purification has often been limited to aHPLC orelectromigration . However, methods developed in 2006 by workers in the lab ofJack L. Arbiser , took advantage of the proximity of the phenolic hydroxyl groups in magnolol, which form a protectablediol , to generate amagnolol acetonide (Figure 1), with a subsequent simple purification viaflash chromatography oversilica 7.
Figure 1
"Magnolol and Honokiol are normally inseparable. Honokiol is easily separable from the protected magnolol acetonide"ynthesis
The synthesis of pure honokiol (Figure 2) involves a Pd-catalyzed Myaura-Suzuki coupling, but this synthesis has afforded only moderate yields8. An older synthetic method involves reaction of
quinol -acetates with theGrignard reagent followed byclaisen rearrangement 9.Figure 2
"Synthetic scheme for total synthesis of honokiol utilizing Pd-catalzyed Suzuki-coupling."
ee also
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Magnolol References
1. Shigemura K, Arbiser JL, Sun SY, Zayzafoon M, Johnstone PA, Fujisawa M, Gotoh A, Weksler B, Zhau HE, Chung LW. Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer. 2007 Apr 1;109(7):1279-89.
2. Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Hideshima H, Shiraishi N, Yasui H, Roccaro AM, Richardson P, Podar K, Le Gouill S, Chauhan D, Tamura K, Arbiser J, Anderson KC. Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis. Blood. 2005 Sep 1;106(5):1794-800. Epub 2005 May 3.
3. Battle TE, Arbiser J, Frank DA. The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood. 2005 Jul 15;106(2):690-7. Epub 2005 Mar 31.
4. Bai X, Cerimele F, Ushio-Fukai M, Waqas M, Campbell PM, Govindarajan B, Der CJ, Battle T, Frank DA, Ye K, Murad E, Dubiel W, Soff G, Arbiser JL. Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem. 2003 Sep 12;278(37):35501-7. Epub 2003 Jun 19.
5. Fukuyama Y, Nakade K, Minoshima Y, Yokoyama R, Zhai H, Mitsumoto Y. Neurotrophic activity of honokiol on the cultures of fetal rat cortical neurons. Bioorg Med Chem Lett. 2002 Apr 22;12(8):1163-6
6. Hu H, Zhang XX, Wang YY, Chen SZ. Honokiol inhibits arterial thrombosis through endothelial cell protection and stimulation of prostacyclin. Acta Pharmacol Sin. 2005 Sep;26(9):1063-8.
7. Amblard F, Delinsky D, Arbiser JL, Schinazi RF. Facile purification of honokiol and its antiviral and cytotoxic properties. J Med Chem. 2006 Jun 1;49(11):3426-7.
8. Esumi T, Makado G, Zhai H, Shimizu Y, Mitsumoto Y, Fukuyama Y. Efficient synthesis and structure-activity relationship of honokiol, a neurotrophic biphenyl-type neolignan. Bioorg Med Chem Lett. 2004 May 17;14(10):2621-5.
9. Takeya, Tetsuya; Okubo, Toru; Tobinaga, Seisho. Showa Coll. Pharm. Sci., Tokyo, Japan. Chemical & Pharmaceutical Bulletin (1986), 34(5), 2066-70.
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