A New Benzofuranone and Anti-HIV Constituents from the Stems of Rhus chinensis

Abstract

A new benzofuran lactone, rhuscholide A (1), was isolated from the stems of Rhus chinensis, together with six known compounds: 5-hydroxy-7-(3,7,11,15-tetramethylhexadeca-2,6,10,11-tetraenyl)-2(3H)-benzofuranone (2), betulin (3), betulonic acid (4), moronic acid (5), 3-oxo-6β-hydroxyolean-12-en-28-oic acid (6) and 3-oxo-6β-hydroxyolean-18-en-28-oic acid (7). Based on 1D, 2D NMR (COSY, HMQC, HMBC) and mass (EI-MS, HR-EI-MS) spectral data, the structure of rhuscholide A was deduced to be 5-hydroxy-3-(propan-2-ylidene)-7-(3,7,11,15-tetramethylhexadeca-2,6,10,11-tetraenyl)-2(3H)-benzofuranone (1). Anti-HIV-1 bioassays in vitro revealed that compound 1 possesses significant anti-HIV-1 activity with an EC₅₀ value of 1.62 μM and a therapeutic index (TI) of 42.40. Compounds 2, 4, 5 and 7 showed moderate anti-HIV-1 activities with EC₅₀ values of 3.70, 5.81, 7.49 and 13.11 μM, respectively.

References

• 1 Schmidt J, Porzel A, Adam G. 3α,20-Dihydroxy-3β,25-epoxylupane, a triterpene from Rhus typhina .  Phytochemistry. 1998;  49 2049-51.
• 2 Shim Y J, Doo H K, Ahn S Y, Kim Y S, Seong J K, Park I S. et al . Inhibitory effect of aqueous extract from the gall of Rhus chinensis on alpha-glucosidase activity and postprandial blood glucose.  J Ethnopharmacol. 2003;  85 283-7.
• 3 Wang R R, Gu Q, Yang L M, Chen J J, Li S Y, Zheng Y T. Anti-HIV-1 activities of extracts from the medicinal plant Rhus chinensis .  J Ethnopharmacol. 2006;  105 269-73.
• 4 Vieira P C, Gottlieb O R, Gottlieb H E. Tocotrienols from Iryanthera grandis .  Phytochemistry. 1983;  22 2281-6.
• 5 Patra A, Chaudhuri S K, Panda S K. Betulin-3-caffeate from Quercus suber. ¹³C-NMR spectra of some lupenes.  J Nat Prod. 1988;  51 217-20.
• 6 Soares F P, Ronconi C AV, Da Cunha E VL, Barbosa-Filho J M, Da Silva M S, Braz-Filho R. Four known triterpenoids isolated from three Brazilian plants: ¹H and ¹³C chemical shift assignments.  Magn Reson Chem. 1998;  36 608-14.
• 7 Wahlberg I, Enzell C R. 3-Oxo -6β-hydroxyolean-12-en-28-oic acid, a new triterpenoid from commercial Tolu balsam .  Acta Chem Scand. 1971;  25 70-6.
• 8 González A G, Amaro J, Fraga B M, Luis J G. 3-Oxo-6β-hydroxyolean-18-en-28-oic acid from Orthopterygium huancuy .  Phytochemistry. 1983;  22 1828-30.
• 9 Kashiwada Y, Hashimoto F, Cosentino L M, Chen C H, Garrett P E, Lee K H. Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents.  J Med Chem. 1996;  39 1016-7.
• 10 Soler F, Poujade C, Evers M, Carry J C, Hénin Y, Bousseau A. et al . Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry.  J Med Chem. 1996;  39 1069-83.
• 11 Pengsuparp T, Cai L N, Fong H HS, Kinghorn A D, Pezzuto J M, Wani M C. et al . Pentacyclic triterpenes derived from Maprounea africana are potent inhibitors of HIV-1 reverse transcriptase.  J Nat Prod. 1994;  57 415-8.
• 12 Beutler J A, Kashman Y, Tischler M, Cardellina II J H, Gray G N, Currens M J. et al . A reinvestigation of Maprounea triterpenes.  J Nat Prod. 1995;  58 1039-46.
• 13 Konoshima T, Yasuda I, Kashiwada Y, Cosentino L M, Lee K H. Anti-AIDS agents, 21. triterpenoid saponins as anti-HIV principles from fruits of Gleditsia japonica and Gymnocladus chinensis, and a structure-activity correlation.  J Nat Prod. 1995;  58 1372-7.
• 14 Kashiwada Y, Wang H K, Nagao T, Kitanaka S, Yasuda I, Fujioka T. et al . Anti-AIDS agents. 30. anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids.  J Nat Prod. 1998;  61 1090-5.
• 15 Mengoni F, Lichtner M, Battinelli L, Marzi M, Mastroianni C M, Vullo V. et al . In vitro anti-HIV activity of oleanolic acid on infected human mononuclear cells.  Planta Med. 2002;  68 106-10.
• 16 Rukachaisirikul V, Pailee P, Hiranrat A, Tuchinda P, Yoosook C, Kasisit J. et al . Anti-HIV-1 protostane triterpenes and digeranylbenzophenone from trunk bark and stems of Garcinia speciosa .  Planta Med. 2003;  69 1141-6.
• 17 Zhang G H, Wang Q, Chen J J, Zhang X M, Tam S C, Zheng Y T. The anti-HIV-1 effect of scutellarin.  Biochem Biophys Res Commun. 2005;  334 812-6.
• 18 Zheng Y T, Zhang W F, Ben K L, Wang J H. In vitro immunotoxicity and cytotoxicity of trichosanthin against human normal immunocytes and leukemia-lymphoma cells.  Immunopharmacol Immunotoxicol. 1995;  17 69-79.