New Polyfunctional Phragmalin Limonoids from Neobeguea mahafalensis ^[*]

Abstract

Neobeguea mahafalensis is used as a medicinal plant in Madagascar. A decoction of the stem bark of this species is reported to treat back pain. Recently, it was reported that a decoction of the root bark, containing two novel phragmalin limonoids as identified active constituents, exhibited an extraordinarily high potency and remarkably long duration in augmenting sexual activity in male rodents.

From the dichloromethane extract of the root barks of N. mahafalensis, nine phragmalin limonoids were isolated, of which eight were novel compounds. The structures were established mainly by extensive use of 2D NMR spectroscopic techniques and high-resolution mass spectrometry. One of the new compounds named dodoguin displayed sleep-inducing activity in Swiss albino mice. The amount of 3–10 mg/kg of this compound induced sleep 18–22 min after its administration with a duration of 16–18 min.

Key words

Neobeguea mahafalensis - Meliaceae - phragmalin limonoids - structure elucidation - 2D NMR - sleep-inducing activity

^* Dedicated to Professor Kurt Hostettmann in recognition of his outstanding contribution to natural product research.

• References

• 1 Leroy JF. Essais de taxonomie syncrétique: Etude sur les Méliaceae de Madagascar. Adansonia 1976; 16: 167-203
• 2 Randrianarivelojosia M, Kotsos M, Mulholland DA. A limonoid from Neobeguea mahafalensis . Phytochemistry 1999; 52: 1141-1143
• 3 Debray MM. Contribution à lʼinventaire des plantes médicinales du Sud-Ouest de Madagascar. In: Debray M, Jacqemin H, Razafindrambao R, editors Contribution à lʼinventaire des plantes médicinales de Madagascar. Paris: ORSTOM; 1971: 21
• 4 Boiteau P, Boiteau M, Allorge-Boiteau L. Dictionnaire des Noms malgaches des Végétaux, Vol. 1. Grenoble: Editions Alzieu; 1999: 436
• 5 Naidoo D, Mulholland DA, Randrianarivelojosia M, Coombes PH. A limonoid from Neobeguea mahafalensis . Biochem Syst Ecol 2003; 31: 1047-1050
• 6 Mulholland DA, Taylor DAH. Limonoid extractives from the genera Capuronianthus, Neobeguea and Quivisianthe . Phytochemistry 1988; 27: 1741-1743
• 7 Liao SG, Chen HD, Yue JM. Plant orthoesters. Chem Rev 2009; 109: 1092-1140
• 8 Luo J, Kong L. [Research progress on phragmalin-type limonoids from genus Chukrasia]. Shenyang Yaoke Daxue Xuebao 2011; 28: 673-679
• 9 Tan QG, Luo XD. Meliaceous limonoids: chemistry and biological activities. Chem Rev 2011; 111: 7437-7522
• 10 Luo J, Wang JS, Wang XB, Huang XF, Luo JG, Kong LY. Chukvelutilides A–F, phragmalin limonoids from the stem bark of Chukrasia tabularis var. velutina . Tetrahedron 2009; 65: 3425-3431
• 11 Wikberg JES, Rasoanaivo P, Benoit R, Razafimahefa AS. Novel compounds and pharmaceutical preparations from Neobeguea mahafalensis extracts and their use for treatment of sexual dysfunction. PCT Int Appl WO 2008145996 A220081204, 2008
• 12 Wikberg JES, Jirgensons A, Liepinsh E. The manufacture and uses of novel limonoid compounds. PCT Int Appl WO 2013110744 A2 20130801, 2013
• 13 Razafimahefa S, Mutulis F, Mutule I, Liepinsh E, Dambrova M, Cirule H, Svalbe B, Yahorava S, Yahorau A, Rasolondratovo B, Rasoanaivo P, Wikberg JES. Libiguins A and B: novel phragmalin limonoids isolated from Neobeguea mahafalensis causing profound enhancement of sexual activity. Planta Med 2014; 80: 306-314
• 14 Coombes PH, Mulholland DA, Randrianarivelojosia M. Phragmalin limonoids from the Madagascan Meliaceae Neobeguea leandriana . J Nat Prod 2003; 66: 735-738
• 15 Connolly JD, Labbe C, Rycroft DS. Tetranortriterpenoids and related substances. Part 20. New tetranortriterpenoids from the seeds of Chukrasia tabularis (Meliaceae); simple esters of phragmalin and 12α-acetoxyphragmalin. J Chem Soc Perkin Trans 1 1978; 1: 285-288
• 16 Yin X, Li X, Hao Y, Zhao Y, Zhou J, Shi H. Xylocarpin H, a limonoid of Xylocarpus granatum, produces antidepressant-like activities in mice. J Behav Brain Sci 2015; 5: 524-532
• 17 Wada K, Yagi M, Kurihara T, Haga M. Studies on the constituents of edible and medicinal plants. III. Effects of seven limonoids on the sleeping time induced in mice by anesthetics. Chem Pharm Bull (Tokyo) 1992; 40: 3079-3080