Anti-HIV-1 Protostane Triterpenes and Digeranylbenzophenone from Trunk Bark and Stems of Garcinia speciosa

Abstract

Three new protostanes, garciosaterpenes A (1), B (2) and C (3), together with a new digeranylbenzophenone, garciosaphenone A (4) were isolated from the ethyl acetate fractions obtained from the crude methanol extracts of the trunk bark and stems of Garcinia speciosa. The structures were elucidated by spectroscopic methods and chemical reactions. Compounds 1 and 3 showed significant inhibitory activities (IC₅₀ 15.5 and 12.2 μg/mL, respectively) against HIV-1 reverse transcriptase and in the syncytium assay (EC₅₀ 5.8 μg/mL with TI 3.4 and 37.0 μg/mL with TI 1.9, respectively). Compound 4 was active in HIV-1 RT assay (IC₅₀ 23.9 μg/mL), but toxic in the syncytium assay. This work represents the first report on the anti-HIV-1 activities of the protostane triterpenes.

Key words

Garcinia speciosa - Guttiferae - protostanes - digeranylbenzophenone - anti-HIV-1 activity

References

• 1 Mahidol University F oundation. Encyclopedia of Medicinal Plants. Volume 4, Bangkok; Amarin Printing and Publishing 2000: 118
• 2 Okudaira C, Ikeda Y, Kondo S, Furuya S, Hirabayashi Y, Koyano T, Saito Y, Umezawa K. Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa .  J Enzym Inhib. 2000;  15 129-38
• 3 Govindachari T R, Kalyanaraman P S, Muthukumaraswamy N, Pai B R. Xanthones of Garcinia mangostana Linn.  Tetrahedron. 1971;  27 3919-26
• 4 Markham K R, Ternai B. ¹³C NMR of flavonoids. II: flavonoids other than flavone and flavonol aglycones.  Tetrahedron. 1976;  32 2607-12
• 5 Barrero A F, Alvarez-Manzaneda R EJ, Alvarez-Mazaneda R R. Achilleol A: a new monocyclic triterpene skeleton from Achillea odorata L.  Tetrahedron Lett. 1989;  30 3351-2
• 6 Akihisa T, Arai K, Kimura Y, Koike K, Kokke W CMC, Shibata T, Nikaido T. Camelliols A-C, three novel incompletely cyclized triterpene alcohols from Sasanqua oil (Camellia sasanqua).  J Nat Prod. 1999;  62 265-8
• 7 Tan G T, Pezzuto J M, Kinghorn A D, Hughes S H. Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.  J Nat Prod. 1991;  54 143-54
• 8 Nara P L, Hatch W C, Dunlop N M, Robey W G. Arthur LO, Gonda MA, Fischinger PJ. Simple, rapid, quantitative, syncytium forming microassay for the detection of human immunodeficiency virus neutralizing antibody.  AIDS Res Hum Retrovir. 1987;  3 283-302
• 9 Kiser R, Makovsky S, Terpening S J, Laing N, Clanton D J. Assessment of a cytoprotection assay for the discovery and evaluation of anti-human immunodeficiency virus compounds utilizing a genetically-impaired virus.  J Virol Meth. 1996;  58 99-109
• 10 Weislow O S, Kiser R, Fine D L, Bader J, Shoemarker R H, Boyd M R. New soluble-formazan assay for HIV-1 cytopathic effects: Application to high-flux screening of synthetic and natural products for AIDS-antiviral activity.  J Natl Cancer Inst. 1989;  81 577-86
• 11 Rukachaisirikul V, Adiar A, Dampawan P, Taylor W C, Turner P C. Lanostanes and friedolanostanes from the pericarp of Garcinia hombroniana .  Phytochemistry. 2000;  55 183-8
• 12 Hou A -J, Fukai T, Shimazaki M, Sakagami H, Sum H -D, Nomura T. Benzophenones and xanthones with isoprenoid groups from Cudrania cochinchinensis .  J Nat Prod. 2001;  64 65-70