Anti HIV-1 Flavonoid Glycosides from Ochna integerrima

Abstract

Bioassay-guided fractionation of the anti-HIV-1 active EtOAc extract from leaves and twigs of Ochna integerrima led to the isolation of five new flavonoid glycosides 1 - 5, five known flavonoids 6 - 10, and two known flavonoid glycosides 11 and 12. Structures were determined based on spectroscopic analyses. 6-γ,γ-Dimethylallyldihydrokaempferol 7-O-β-D-glucoside (1), 6-γ,γ-dimethylallylquercetin 7-O-β-D-glucoside (3), 6-(3-hydroxy-3-methylbutyl)taxifolin 7-O-β-D-glucoside (4), 6-(3-hydroxy-3-methylbutyl)quercetin 7-O-β-D-glucoside (5), and 6-γ,γ-dimethylallyltaxifolin 7-O-β-D-glucoside (11) showed anti-HIV-1 activities in the syncytium assay using the ^ΔTat/revMC99 virus and the 1A2 cell line system with EC₅₀ values ranging from 14.0 - 102.4 μg/mL. Furthermore, ochnaflavone 7″-O-methyl ether (7) and 2″, 3″-dihydroochnaflavone 7″-O-methyl ether (8) were very active; they exerted activities in the syncytium assay with EC₅₀ values of 2.0 and 0.9 μg/mL, respectively, and likewise inhibited HIV-1 reverse transcriptase (RT) with IC₅₀ values of 2.0 and 2.4 μg/mL, respectively.

Abbreviations

AZT: azidothymidine

CC: column chromatography

prep. TLC: preparative thin layer chromatography

Ochna integerrima - flavonoid glycosides - Ochnaceae - anti-syncytium activity - anti-HIV-1 RT activity

References

• 1 Kamil M, Khan N A, Ilyas M, Rahman W. Biflavones from Ochnaceae - a new biflavone from Ochna pumila .  Ind J Chem. 1983;  22B 608.
• 2 Kamil M, Khan N A, Alam M S, Ilyas M. A biflavone from Ochna pumila .  Phytochemistry. 1987;  26 1171-3.
• 3 Messanga B B, Tih R G, Kimbu S F, Sondengam B L, Martin M T, Bodo B. Calodenone, a new isobiflavonoid from Ochna calodendron .  J Nat Prod. 1992;  55 245-8.
• 4 Messanga B B, Tih R G, Sondengam B L, Martin M T, Bodo B. Biflavonoids from Ochna calodendron .  Phytochemistry. 1994;  35 791-4.
• 5 Sibanda S, Nyanyira C, Nicoletti M, Galeffi C. Ochnabianthrone: a trans-9, 9′-bianthrone from Ochna pulchra .  Phytochemistry. 1990;  29 3974-6.
• 6 Nia M, Gunasekar D. A new isoflavone from root bark of Ochna squarrosa .  Fitoterapia. 1992;  63 249-50.
• 7 Smitinand T, Larsen K. Flora of Thailand, Vol 2. Bangkok; Tistr Press 1981.
• 8 Perry L M. Medicinal plants of East and Southeast Asia. Boston; The MIT Press 1980
• 9 Likhitwitayawuid K, Rungserichai R, Ruangrungsi N, Phadungcharoen T. Flavonoids from Ochna integerrima .  Phytochemistry. 2001;  56 353-7.
• 10 Kaewamatawong R, Likhitwitayawuid K, Ruangrungsi N, Takayama H, Kitajima M, Norio A. Novel biflavonoids from stem bark of Ochna integerrima .  J Nat Prod. 2002;  65 1027-9.
• 11 Ichino C, Kiyohara H, Soonthorncharoennon N, Chaukul W, Ishiyama A, Sekiguchi H. et al . Antimalarial activity of biflavonoids from Ochna integerrima .  Planta Med. 2006;  72 611-4.
• 12 Rukachaisirikul V, Pailee P, Hiranrat A, Tuchinda P, Yoosook C, Kasisit J. et al . Anti-HIV-1 protostanes and digeranylbenzophenone from trunk bark and stems of Garcinia speciosa .  Planta Med. 2003;  69 1141-6.
• 13 Tuchinda P, Saiai A, Pohmakotr M, Yoosook C, Kasisit J, Napaswat C. et al . Anti-HIV-1 cycloartanes from leaves and twigs of Gardenia thailandica .  Planta Med. 2004;  70 366-70.
• 14 Kachroo P K, Razdan T K, Qurishi M A, Khuroo M A, Koul S, Dhar K L. Two isoflavones from Iris kashmiriana .  Phytochemistry. 1991;  29 1014-6.
• 15 Khalil S A, Eisawi D A. New isoflavones from Iris nigricans .  J Nat Prod. 1994;  57 201-5.
• 16 Evans W H, McGookin A, Jurd L, Robertson A, Williamson W RN. Vitexin. Part I. J Chem Soc 1957: 3510-23.
• 17 Tan T G, 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.
• 18 Nara P L, Hatch W C, Dunlop N M, Robey W G, Arthur L O, Gonda M A. et al . Simple, rapid, quantitative, syncytium forming microassay for the detection of human immunodeficiency virus neutralizing antibody.  AIDS Res Human Retrovir. 1987;  3 283-302.
• 19 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.
• 20 Chou T -C, Talalay P. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors.  Adv Enzyme Regul. 1984;  22 27-55.
• 21 Mabry T J, Markham K R, Thomas M B. The systematic identification of flavonoids. New York; Springer-Verlag 1970: 44.
• 22 Wu T S, Hsu M Y, Kuo P C, Sreenivasulu B, Damu A G, Su C R. et al . Constituents from the leaves of Phellodendron smurensa var. wilsonii and their bioactivity.  J Nat Prod. 2003;  66 1207-11.
• 23 Pawan K G. NMR spectroscopy in the structural elucidation of oligosaccharides and glycosides.  Phytochemistry. 1992;  31 3307-30.
• 24 John L I. New 3-hydroxyflavanone (dihydroflavonol)phytoalexins from the papilionate legume Shuteria vestita .  J Nat Prod. 1986;  49 631-8.
• 25 Calis I, Heilmann J, Tasdemir D, Linden A, Ireland C M, Sticher O. Flavonoid, iridoid and lignan glycosides from Putoria calabrica .  J Nat Prod. 2001;  64 961-4.
• 26 Agrawal P K. Carbon-13 NMR of Flavonoids. Amsterdam; Elsevier Science 1989: 150-8.
• 27 Markham K R, Chari V M, Mabry T J. The Flavonoids: Advances in research. London; Chapman & Hall 1982: 19-134
• 28 Meragelman K M, McKee T C, Boyd M R. Anti-HIV prenylated flavonoids from Monotes africanus .  J Nat Prod. 2001;  64 546-8.
• 29 McKee T C, Bokesch H R, McCormick J L, Rashid M A, Spielvogel D, Gustafson K R. et al . Isolation and characterization of new anti-HIV and cytotoxic leads from plants, marine and microbial organisms.  J Nat Prod. 1997;  60 431-8.