New Structurally Diverse Limonoids from the Seeds of Khaya senegalensis

Abstract

Twelve new limonoids (khasenegasins O–Z; 1–12) with three different kinds of skeletons, including eight mexicanolides, two gedunins, and two andirobins, together with four known limonoids (13–16) were isolated from the seeds of Khaya senegalensis. Their structures were determined by extensive spectroscopic analyses (HR-ESI-MS, 1D/2D NMR), and the absolute configurations of 1 and 2 were established by the electronic circular dichroism exciton chirality method. Moreover, a new andirobin-type limonoid (12) showed significant neuroprotective activity against glutamate-induced injury in primary rat cerebellar granule neuronal cells with increased viability of 83.3 ± 6.0 % at 10 µM and 80.3 ± 3.2 % at 1 µM.

Key words

Khaya senegalensis - Meliaceae - limonoids - ECD exciton chirality - neuroprotective activity

^* These authors contributed equally to this work.

• References

• 1 Fang X, Di YT, Hao XJ. The advances in the limonoid chemistry of the Meliaceae family. Curr Org Chem 2011; 15: 1363-1391
• 2 Tan QG, Luo XD. Meliaceous limonoids: chemistry and biological activities. Chem Rev 2011; 111: 7437-7522
• 3 Adesogan EK, Taylor DAH. Extractives from Khaya senegalensis (Desr.) A. Juss. J Chem Soc C 1968; 1974-1981
• 4 Olmo LRV, da Silva MFdGF, Fo ER, Vieira PC, Fernandes JB, Marsaioli AJ, Pinheiro AL, Vilela EF. Rearranged limonoids from Khaya senegalensis . Phytochemistry 1996; 42: 831-837
• 5 Khalid SA, Friedrichsen GM, Kharazmi A, Theander TG, Olsen CE, Christensen SB. Limonoids from Khaya senegalensis . Phytochemistry 1998; 49: 1769-1772
• 6 Abdelgaleil SAM, Iwagawa T, Doe M, Nakatani M. Antifungal limonoids from the fruits of Khaya senegalensis . Fitoterapia 2004; 75: 566-572
• 7 Adesogan EK, Powell JW, Taylor DAH. Extractives from the seed of Khaya senegalensis . J Chem Soc C 1967; 554-556
• 8 Watt JM, Breyer-Brandwijk MG. The medicinal and poisonous Plants of southern and eastern Africa. 2nd ed.. London, Edinburgh: Livingstone; 1962: 205-206
• 9 Abdelgaleil SAM, Doe M, Morimoto Y, Nakatani M. Rings B,D-seco limonoids from the leaves of Swietenia mahogani . Phytochemistry 2006; 67: 452-458
• 10 Lin LG, Yang XZ, Tang CP, Ke CQ, Zhang JB, Ye Y. Antibacterial stilbenoids from the roots of Stemona tuberosa . Phytochemistry 2008; 69: 457-463
• 11 Lin BD, Yuan T, Zhang CR, Dong L, Zhang B, Wu Y, Yue JM. Structurally diverse limonoids from the fruits of Swietenia mahagoni . J Nat Prod 2009; 72: 2084-2090
• 12 Zhang WM, Liu JQ, Deng YY, Xia JJ, Zhang ZR, Li ZR, Qiu MH. Diterpenoids and limonoids from the leaves and twigs of Swietenia mahagoni . Nat Prod Bioprospect 2014; 4: 53-57
• 13 Nakatani M, Abdelgaleil SA, Kassem SM, Takezaki K, Okamura H, Iwagawa T, Doe M. Three new modified limonoids from Khaya senegalensis . J Nat Prod 2002; 65: 1219-1221
• 14 Nakatani M, Abdelgaleil SA, Kurawaki J, Okamura H, Iwagawa T, Doe M. Antifeedant rings B and D opened limonoids from Khaya senegalensis . J Nat Prod 2001; 64: 1261-1265
• 15 Abdelgaleil SAM, Nakatani M. Antifeeding activity of limonoids from Khaya senegalensis . J Appl Entomol 2003; 127: 236-239
• 16 Abdelgaleil SAM, Okamura H, Iwagawa T, Sato A, Miyahara I, Doe M, Nakatani M. Khayanolides rearranged phragmalin limonoid antifeedants from Khaya senegalensis . Tetrahedron 2001; 57: 119-126
• 17 Li H, Li Y, Wang XB, Pang T, Zhang LY, Luo J, Kong LY. Mexicanolide limonoids with in vitro neuroprotective activities from seeds of Khaya senegalensis . RSC Adv 2015; 5: 40465-40474
• 18 Li MY, Yang XB, Pan JY, Feng G, Xiao Q, Sinkkonen J, Wu J. Granatumins A–G, limonoids from the seeds of a Krishna mangrove, Xylocarpus granatum . J Nat Prod 2009; 72: 2110-2114
• 19 Shen LR, Dong M, Guo D, Yin BW, Zhang ML, Shi QW, Huo CH, Kiyota H, Suzuki N, Cong B. Xylomexicanins A and B, new 14,15-mexicanolides from seeds of the Chinese mangrove Xylocarpus granatum . Z Naturforsch C 2009; 64: 37-42
• 20 Inoue T, Matsui Y, Kikuchi T, In Y, Muraoka O, Yamada T, Tanaka R. Carapanolides C–I from the seeds of andiroba (Carapa guianensis, Meliaceae). Fitoterapia 2014; 96: 56-64
• 21 Taylor DAH. The Chemistry of the Limonoids from Meliaceae. In: Herz W, Grisebach H, Kirby GW. eds. Progress in the Chemistry of organic natural Products. New York: Springer; 1984: 1-102
• 22 Luo J, Wang JS, Wang XB, Luo JG, Kong LY. Phragmalin-type limonoid orthoesters from Chukrasia tabularis var. velutina . Chem Pharm Bull 2011; 59: 225-230
• 23 Lavie D, Levy EC, Rosito C, Zelnik R. Studies on tetranortriterpenoids from Cedrela augustifolia Sessée and Moc. Tetrahedron 1970; 26: 219-226
• 24 Garcez FR, Garcez WS, Tsutsumi MT, Roque NF. Limonoids from Trichilia elegans ssp. elegans . Phytochemistry 1997; 45: 141-148
• 25 Khalid SA, Duddeck H, Gonzalez-Sierra M. Isolation and characterization of an antimalarial agent of the neem tree Azadirachta indica . J Nat Prod 1989; 52: 922-926
• 26 Mitsui K, Saito H, Yamamura R, Fukuya H, Hitotsuyanagi Y, Takeya K. Hydroxylated gedunin derivatives from Cedrela sinensis . J Nat Prod 2006; 69: 1310-1314
• 27 Akisanya A, Arene E, Bevan C, Ekong D, Nwaji M, Okogun J, Powell J, Taylor D. West African timbers. Part XII. The inter-relation of gedunin and khivorin. J Chem Soc C 1966; 506-509
• 28 Bickii J, Njifutie N, Foyere JA, Basco LK, Ringwald P. In vitro antimalarial activity of limonoids from Khaya grandifoliola C.D.C. (Meliaceae). J Ethnopharmacol 2000; 69: 27-33
• 29 Li Y, Lu Q, Luo J, Wang J, Wang X, Zhu M, Kong LY. Limonoids from the stem bark of Khaya senegalensis . Chem Pharm Bull 2015; 63: 305-310
• 30 Saewan N, Sutherland JD, Chantrapromma K. Antimalarial tetranortriterpenoids from the seeds of Lansium domesticum Corr. Phytochemistry 2006; 67: 2288-2293
• 31 Tanaka Y, Sakamoto A, Inoue T, Yamada T, Kikuchi T, Kajimoto T, Muraoka O, Sato A, Wataya Y, Kim HS, Tanaka R. Andirolides H–P from the flower of andiroba (Carapa guianensis, Meliaceae). Tetrahedron 2012; 68: 3669-3677
• 32 Ravangpai W, Sommit D, Teerawatananond T, Sinpranee N, Palaga T, Pengpreecha S, Muangsin N, Pudhom K. Limonoids from seeds of Thai Xylocarpus moluccensis . Bioorg Med Chem Lett 2011; 21: 4485-4489
• 33 Adesogan EK, Taylor DAH. Limonoid extractives from Khaya ivorensis . J Chem Soc C 1970; 1710-1714
• 34 Jeong GS, Byun E, Li B, Lee DS, An RB, Kim YC. Neuroprotective effects of constituents of the root bark of Dictamnus dasycarpus in mouse hippocampal cells. Arch Pharm Res 2010; 33: 1269-1275