Quassinoid Explained

Quassinoids are degraded triterpene lactones (similar to limonoids) of the Simaroubaceae plant family grouped into C-18, C-19, C-20, C-22 and C-25 types.^[1] The prototypical member of the group, quassin, was first described in the 19th century from plants of the genus Quassia from which it gets its name.^[2] It was isolated in 1937,^[3] and its structure elucidated in 1961.^[4]

Sources

More than 200 currently-known quassinoids have been isolated and identified from various species of simaroubaceae family.^[5]

Quassinoids can also be extracted from various Simaroubaceae family species such as; Ailanthus excelsa,^[6] Ailanthus vilmoriniana,^[7] (the fruits of) Brucea javanica,^[8] Hannoa klaineana,^{[9] [10]} Pierreodendron kerstingii,^[11] Quassia africana,^{[12] [13]} Quassia amara,^{[14] [15]} (the wood of) Picrasma ailanthoides,^[16] Picrasma javanica,^[17] Picrolemma pseudocoffea,^[18] Simaba guianensis,^[19] and Simaruba glauca.^[20]

They are found in species from American and West African genera (belonging mainly to the tribe Simaroubeae) and from the East African and Asian genera (belonging mainly to Picrasmeae and Soulameae tribes).^[21]

Uses

They are a biologically potent class of natural products, possessing antimalarial,^{[15] [22]} antifeedant,^[23] insecticidal,^[24] anti-inflammatory,^[25] and anticancer (or anti-leukemic)^{[11] [26] [27]} properties. The quassinoid bruceantin reached two separate phase II clinical trials in 1982^[28] and 1983.^[29]

Other quassinoids include:^[30]

• Bruceanols
• Bruceolide
• Eurycomanone
• Gutolactone
• Isobrucein A
• Neoquassin
• Nigakihemiacetal A
• Odyendanol^[10]
• Picrasinol D^[16]
• Quassimarin
• Samaderines
• Simalikalactones (including simalikalactones A, B, C,^[13] simalikalactone D,^{[12] [14]} and simalikalactone E^[31])

Other sources

• Z. Guo, S. Vangapandu, R.W. Sindelar, L.A. Walker, R.D. Sindelar., Biologically active quassinoids and their chemistry: potential leads for drug design, Frontier. Med. Chem., 4 (2009), pp. 285-308

Notes and References

1. Book: 10.1016/S1572-5995(06)80032-3 . Quassinoids: Structural Diversity, Biological Activity and Synthetic Studies . Studies in Natural Products Chemistry . 2006 . Curcino Vieira . Ivo J. . Braz-Filho . Raimundo . 33 . 433–492 . 978-0-444-52717-2 .
2. Quassin I. The preparation and purification of quassin and neoquassin, with information concerning their molecular formulas . Winckler, F. L. . Rep. Pharm. . 1835 . 4 . 85.
3. E.P. Clark, J. Amer. Chem. Soc. (1937)
4. Valenta . Z. . Papadopoulos . S. . Podešva . C. . Quassin and Neoquassin . Tetrahedron . 1961 . 15 . 1–4 . 100–110 . 10.1016/0040-4020(61)80013-6.
5. Curcino Vieira . I.J. . Braz-Filho . R. . _structural diversity, biological activity and synthetic studies_ . Stud. Nat. Prod. Chem. . 2006 . 33 . 433–492. 10.1016/S1572-5995(06)80032-3 .
6. Joshi . B.C. . Pandei . A. . Sharma . R.P. . Khare . A. . Quassinoids from Ailanthus excelsa . Phytochemistry . 2003 . 62 . 4 . 579–584. 10.1016/S0031-9422(02)00493-4 . 12560029 . 2003PChem..62..579J .
7. Takeya . K. . Kobata . H. . Ozeki . A. . Morita . H. . Itokawa . H. . Quassinoids from Ailanthus vilmoriniana . Phytochemistry . 1998 . 48 . 3 . 565. 10.1016/S0031-9422(97)00893-5 . 1998PChem..48..565T .
8. Anderson . M.M. . O’Neill . M.J. . Phillipson . J.D. . Warhurst . D.C. . In vitro cytotoxicity of a series of quassinoids from Brucea javanica fruits against KB cells . Planta Med. . 1991 . 57 . 1 . 62–64. 10.1055/s-2006-960020 . 2062960 . 21082303 .
9. Lumonadio . L. . Atassi . G. . Vanhaelen . M. . Vanhaelen-Fastre . R. . 1991 . J. Ethnopharmacol. . Antitumor activity of quassinoids from Hannoa klaineana . 31 . 1 . 59–65. 10.1016/0378-8741(91)90144-3 . 2030594 .
10. Donkwe . Suzye Mireille Moladje . Happi . Emmanuel Ngeufa . Wansi . Jean Duplex . Lenta . Bruno Ndjakou . Devkota . Krishna Prasad . Neumann . Beate . Stammler . Hans-Georg . Sewald . Norbert . Oxidative burst inhibitory and cytotoxic activity of constituents of the fruits of Odyendyea gabonensis . Planta Med. . December 2012 . 78 . 18 . 1949–56 . 10.1055/s-0032-1327878 . 23136063.
11. Kupchan . S.M. . Lacadie . J.A. . Dehydroailanthinone, a new antileukemic quassinoid from Pierreodendron kerstingii . J. Org. Chem. . 1975 . 40 . 5 . 654–656 . 10.1021/jo00893a024 . 1133628 .
12. Apers . S. . Cimanga . K. . Vanden Berghe . D. . Van Meenen . E. . Longanga . A.O. . Foriers . A. . Vlietinck . A. . Pieters . L. . Antiviral activity of Simalikalactone D, a quassinoid from Quassia africana . Planta Med. . 2002 . 68 . 1 . 20–24. 10.1055/s-2002-19870 . 11842321 . 260284246 .
13. Tresca . J.P. . Alais . L. . Polonsky . J. . Bitter constituents of Quassia africana Baill. (Simarubaceae). Simalikalactones A, B, C and D and simalikaliacetal A. . C. R. Acad. Sci. Paris . 1971 . 273 . 601.
14. Bertani . S. . Houël . E. . Stien . D. . Chevolot . L. . Jullian . V. . Garavito . G. . Bourdy . G. . Deharo . E. . Simalikalactone D is responsible for the antimalarial properties of an amazonian traditional remedy made with Quassia amara L. (Simaroubaceae) . J. Ethnopharmacol. . 2006 . 108 . 1 . 155–157. 10.1016/j.jep.2006.04.017 . 16730421 .
15. Bertani . S. . Houël . E. . Stien . D. . Chevolot . L. . Jullian . V. . Garavito . G. . Bourdy . G. . Deharo . E. . New findings on simalikalactone D, an antimalarial compound from Quassia amara L. (Simaroubaceae) . Exp. Parasitol. . 2012 . 130 . 4 . 341–347. 10.1016/j.exppara.2012.02.013 . 22374406 .
16. Daido . M. . Fukamiya . N. . Okano . M. . Picrasinol D, a new quassinoid from the stem wood of Picrasma ailanthoides . J. Nat. Prod. . 1995 . 58 . 4 . 605–608. 10.1021/np50118a022 .
17. Koike . K. . Ishi . K. . Mitsunaga . K. . Ohmoto . T. . Quassinoids from Picrasma javanica . Phytochemistry . 1991 . 30 . 3 . 933–936. 10.1016/0031-9422(91)85282-5 . 1991PChem..30..933K .
18. Moretti . C. . Polonsky . J. . Vuilhorgne . M. . Prange . T. . Isolation and structure of sergeolide, a potent cytotoxic quassinoid from Picrolemma pseudocoffea . Tetrahedron Lett . 1982 . 23 . 6 . 647. 10.1016/S0040-4039(00)86912-9 .
19. Cabral . J.A. . McChesney . J.D. . Milhous . W.K. . A new anti-malarial quassinoid from Simaba guianensis . J. Nat. Prod. . 1993 . 56 . 11 . 1954–1961 . 10.1021/np50101a014 . 8289064 .
20. Moron . J. . Merrien . M.A. . Polonsky . J. . On the biosynthesis of quassinoids Simaruba glauca (Simarubaceae). . Phytochemistry . 1971 . 10 . 585. 10.1016/S0031-9422(00)94702-2 .
21. Simão . Sheila M. . Barreiros . Euclides L. . das G.F. Da Silva . M.Fátima . Gottlieb . Otto R. . Chemogeographical evolution of quassinoids in simaroubaceae . Phytochemistry . 1991 . 30 . 3 . 853–865 . 10.1016/0031-9422(91)85267-4. 1991PChem..30..853S .
22. Muhammad, I. . Antimalarial quassinoids: Past, present and future . Samoylenko, V. . Expert Opin Drug Discov . 2007 . 2 . 8 . 1065–84 . 10.1517/17460441.2.8.1065 . 23484873 . 24497786 .
23. Leskinen, V. . Antifeedant activity of quassinoids . Polonsky, J. . Bhatnagar, S. . J. Chem. Ecol. . 1984 . 10 . 10 . 1497–507 . 10.1007/BF00990319 . 24318349 . 1984JCEco..10.1497L . 21117128 .
24. Fang, X. . Di, Y. T. . Xhang, Y. . Xu, Z. P. . Lu, Y. . Chen, Q. Q. . Zheng, Q. T. . Hao, X. J. . Angew. Chem. Int. Ed. . 2015 . 54 . 19 . 5592–5 . 10.1002/anie.201412126 . 25810025 . Unprecedented Quassinoids with Promising Biological Activity from Harrisonia perforata.
25. Hall, I. H. . Anti-inflammatory Agents III: Structure–Activity Relationships of Brusatol and Related Quassinoids . Lee, K. H. . Imakura, Y. . Okano, M. . Johnson, A. . J. Pharm. Sci. . 1983 . 72 . 11 . 1282–4 . 10.1002/jps.2600721111 . 6417321 .
26. Fukamiya, N. . Lee, K.H. . Muhammad, I. . Murakami, C. . Okano, M. . Harvey, I. . Pelletier, J. . Cancer Letters . 2005 . 220 . 1 . 37–48 . 10.1016/j.canlet.2004.04.023 . 15737686 . Structure–activity relationships of quassinoids for eukaryotic protein synthesis.
27. Fiaschetti . G. . Grotzer . M.A. . Shalaby . T. . Castelletti . D. . Arcaro . A. . _from traditional drugs to new cancer therapists_ . Curr. Med. Chem. . 2011 . 18 . 3 . 316–328 . 10.2174/092986711794839205 . 21143123 .
28. Wiseman, C. L. . Phase II trial of bruceantin in metastatic breast carcinoma . Yap, H. Y. . Bedikian, A. Y. . Bodey, G. P. . Blumenchein, G. R. . Am. J. Clin. Oncol. . 1982 . 5 . 4 . 389–91 . 10.1097/00000421-198208000-00007 . 7113961 . 27632884 .
29. Arsenau, J. C. . Wolter, J. M. . Kuperminc, M. . Ruckdeschel, J. C. . Invest. New Drugs . 1983 . 1 . 239 . Anti–inflammatory agents III: Structure–activity relationships of brusatol and related quassinoids.
30. Web site: Quassinoid . Chemical Entities of Biological Interest (ChEBI).
31. Cachet . N. . Valentin . A. . Jullian . V. . Stien . D. . Houël . E. . Gornitzka . H. . Fillaux . J. . Chevalley . S. . Hoakwe . F. . Bertani . S. . Bourdy . G. . Deharo . E. . Antimalarial activity of simalikalactone E, a new quassinoid of Quassia amara L. (Simaroubaceae) . Antimicrob. Agents Ch. . 2009 . 53 . 10 . 4393–4398. 10.1128/AAC.00951-09 . 19667291 . 2764154 .