Chemical Constituents Of Benzoin And Olibanum And Their Antitumor Activity

Styrax tonkinensis (Pier.) Craib (Styracaceae) is an arbor distributed in severalregions of South-East Asia. Its resin, benzoin, has been used as an expectorant inChina. Boswellia carterii Birdw (Burseraceae) is also an arbor distributed in Somaliaand Ethiopia. Its resin, olibanum, was used to treat aoronary disease, angina pectoris,and ulcer in China. Based on the review on the chemical constituents andpharmacological research of Styrax and Boswellia, the chemical constituents and theirantitumor activities of the two resins were researched.By means of many different chromatographic methods such as silica gel,Sephadex LH-20, reversed phase ODS column chromatography and preparative TLC,17 compounds were isolated from benzoin. By physico-chemical data and spectralmethods, all the compounds were identified as 6β-hydroxy-3-oxo-11α,12α-epoxyolean-28, 13β-olide (1), 3β, 6β-dihydroxy-11α, 12α-epoxyolean-28,13β-olide (2), 3β, 6β-dihydroxy-11-oxo-olean-12-en-28-oic acid (3), 3β-hydroxy-12-oxo-13Hα-olean-28, 19βolide (4), 19α-hydroxy-3-oxo-olean-12-en-28-oic acid(5), 6β-hydroxy-3-oxo-olean-12-en-28-oic acid (6), sumaresinolic acid (7),siaresinolic acid (8), oleanolic acid (9), trans-(tetrahydro-2-(4-hydroxy-3-meth0xyphenyl)-5-oxofuran-3-y1)methyl benzoate (10), 3-(4-hydroxy-3-methoxypheny1)-2-oxopropyl benzoate (11), 4-((E)-3-ethoxyprop-1-enyl)-2-methoxyphenol(12), benzoic acid (13), vanillin (14), dehydrodivanillin (15), vanillic acid (16) andconiferyl aldehyde (17). Among them, compounds 1-4, 10 and 11 were determined asnew compounds and compound 12 was a new natural product.By means of many different chromatographic methods such as silica gel,Sephadex LH-20, reversed phase ODS column chromatography and preparative TLC,22 compounds were isolated from olibanum. 21 of them were authenticated byphysico-chemical data and spectral methods, and they wereα-amyrin (B1),β-boswellic acid (B2), acetyl 11α-methoxy-β-boswellic acid (B3), 11-keto-β-boswellic acid (B4), acetyl 11-keto-β-boswellic acid (BS), 9,11-dehydro-β-boswellic acid (B6), acetylβ-boswellic acid and acetylα-boswellic acid (B7),α-boswellic acid (BS), 9,11-dehydro-α-boswellic acid (B9), 3β20β-18Hα-ursanediol(B10), acetylα-elemolic acid (B11), 3β-hydroxytirucalla-8,24-dien-21-oic acid (B12),elemonic acid (B13), 3-oxotirucalla-7, 9(11), 24-trien-21-oic acid (B14), 3α- hydroxytirucalla-7, 24-dien-21-oic acid (B15), 3α-hydroxytirucall-24-en-21-oic acid(B16), incensole (B17), acetyl incensole (B18), incensole-oxide (B19), acetylincensole-oxide (B20) andα-glyceryl palmitate (B21). Among them, compounds B10and B14 were determined as new compounds.The antitumor activities of the triterpenes and diterpenes isolated from benzoinand olibanum were researched. By testing in human leukemia HL-60 cells, it wasfound that all triterpenoids 1-9 isolated from benzoin inhibited cell growth withdifferent activity. Compound 9 was the most potent with an IG₅₀ of 8.9μM, whilecompound 3 was the least effective growth inhibitor with an IG₅₀ of 99.4μM. The celldifferentiation ability of these triterpenoids was measured in HL-60 cells using NBTreduction assay. Only compound 3 showed differentiation induction in HL-60 cells atnon-toxic concentrations. Tetracyclic triterpenoids (B11, B13, B15), pentacyclictriterpenoids (B3, B4, B5, B6, B7, B9) and diterpenoid (B18) isolated from olibanumwere effective cell growth inhibitors with IG₅₀s ranged from 12.3μM to 21.8μM. Theapoptotic effects in HL-60 cells were also examined by morphological observationafter AO and EB staining. All these triterpenoids induced HL-60 cells undergoapoptosis in a dose-and time-dependent manner. Some triterpenes with stronger cellgrowth inhibition ability in HL-60 cells were selected to test their growth inhibitoryeffect in PC-3 cells. The data indicated that compounds B3-5, B7 and B11 hadinhibitory effect on growth of PC-3 cells, with the IG₅₀s ranged from 16.5 to 62.3μM.Based on the growth inhibition activity, the structure-activity relationship oftriterpenes was discussed.In term of the research on tirucallane-type triterpenoid isolated from olibanumadding to the related literatures, an overview on the spectral and structuralcharacteristics of tirucallane-type tfiterpenoid was taken.