Nguyen Thanh Tam

Synthesis and Cytotoxic Activity of Ursolic Acid Derivatives

10-15 Fourteen ursolic acid derivatives, among them four novel compounds, were synthesized by modification either at the C-3, C-28 or both positions. The cytotoxic activity of the obtained derivatives was evaluated against the four human cancer cell lines KB (human mouth epidermal carcinoma), HepG2 (human hepatocellular carcinoma), MCF7 (human breast carcinoma) and Lu (human lung carcinoma). As the result, compounds 7and 8were from two to three times more active than ursolic acid on all four tested cell lines. This is the first report on cytotoxic effects of the synthetized ursolic acid derivatives 4, 8, and . Graphical Abstract Synthesis and Cytotoxic Activity of Ursolic Acid Derivatives

INVESTIGATING THE ANTI-INFLAMMATORY ACTIVITY OF AN ETHANOLIC EXTRACT FROM ARTOCARPUS TONKINENSIS LEAVES USING A COLLAGEN ANTIBODY-INDUCED ARTHRITIC MOUSE MODEL

This study was contrived for evaluating the in vitro and in vivo anti-inflammatory effects of an aqueous ethanolic leaf extract of the Vietnamese Artocarpustonkinensis A. Chev. exGagnep. usinglipopolysaccharide-stimulated RAW 264.7 macrophages and a collagen antibody-induced arthritic mouse model as well. The obtained results here demonstrate that the 70 % ethanolic leaf extract of A. tonkinensis(AT2), traditionally used in Vietnamese folk medicine for treating arthritic symptoms, has beneficial effects on pro-inflammatory cytokine inhibition and in an experimental arthritic mouse model.LPS-stimulated RAW 264.7 macrophages treated with AT2 showed a significant decrease in the production of IL-6 and TNF at concentrations of 12.5, 25 and 50 μg/mL (P < 0.05), indicating its potential anti-inflammatory properties. The treatment of CAIA mice with AT2 also led to diminish the incidence of arthritis at doses of 200 and 300 mg/kg body weight.

Chemical constituents from the leaves of Pinus dalatensis Ferré

Abstract A phytochemical study of n-hexane and ethyl acetate extracts of Pinus dalatensis Ferré leaves led to the isolation of 11 compounds, including one caryolane sesquiterpenoid (1), five labdane diterpenoids (2, 3, 4, 5, 6), one serratane triterpenoid (7), one diacylated flavonoid glucoside (8), one stilbenoid (9) and two sterols (10, 11). The structural characterisation of the isolated compounds was elucidated by spectroscopic data and comparison with the literature report on the chemical constituents from Pinus dalatensis Ferré. Futhermore, three compounds 1, 4 and 6 were obtained for the first time from the genus Pinus. Besides, compounds (2, 3, 5, 8, 9) were also subjected to cytotoxicity effect on SK-LU-1, MCF-7 and Hep-G2 cell lines, but only compound 9 expressed activities with IC50 values of 141.22, 127.81 and 166.84 μM, respectively.

Anti-proliferative diterpenes from Dacrycarpus imbricatus

Abstract A new diterpene, cassipouryl hexadecanoate (2), in addition to the cassipourol (1) and four terpenes (3–6) were isolated from the twigs and leaves of Dacrycarpus imbricatus (Blume) de Laub. The structures of the two monocyclic diterpenes (1, 2), were elucidated on the basic of 1D and 2D NMR spectroscopic data and compared with the literature. These two monocyclic diterpenes (1, 2) were tested for their anti-proliferative activity on acute myeloid leukemia (OCI-AML) cells. The results showed that 1 had significantly anti-proliferative activity whereas 2 was weakly active.

Cytotoxic Alkaloids from Stephania dielsiana

The genus Stephania belongs to the family Menispermaceae, widely distributed in Africa, India, Southeast Asia, and the northern and eastern parts of Australia. They comprise more than 60 species, in which several Stephania genus were used as folk remedies [1]. Many alkaloids with interesting pharmacological activity were isolated from this genus [2]. Stephania dielsiana Y. C. Wu is a medicinal plant, which has been used in Vietnamese traditional medicine as an analgesic and sedative and for the treatment of neuralgia, stomachache, and arthritis. There are some reports on the chemical constituents of the tubers of this species [3–5]. Some isolated compounds showed antimicrobial, hypotensive, and anticarcinogenic activities [6, 7]. In this study, seven alkaloids, tetrahydropalmatine (1), stephanine (2), crebanine (3), O-methylbulbocapnine (4), oxostephanine (5), palmatine (6), and thailandine (7), were isolated from the leaves of this plant. The structures of these alkaloids were elucidated by spectroscopic methods, including MS, PMR, 13C NMR, HSQC, and HMBC and compared with the reported references. Among them, compounds 4, 6, and 7 were isolated for the first time from this plant. Some alkaloids from Stephania were investigated for their cytotoxic activities against some kinds of mammalian cancer cell lines such as KB, HepG2, MRC-5, MCFGLC4, GLC4/Adr, K562, and K562/Adr [2, 8–10]. Herein, the isolated alkaloids 1–7 were tested for their cytotoxic activities against human breast cancer cell line (BT474) and human colon cancer cell line (HCT116). Docetaxel was used as positive control [11]. Testing was carried out in triplicate for each compound and concentration. Then the results were analyzed and processed statistically. The IC50 values are listed in Table 1. All tested compounds exhibited antiproliferative activities against two cancer cells tested. Compounds 2 and 3 demonstrated potent cytotoxicity against BT474 cell with IC50 of 1.55 and 1.58 g/mL, respectively. Compound 7 showed strong cytotoxicity against both cell lines (IC50 = 1.89 and 2.76 g/mL, respectively).

Chemical constituents and their biological activity of Pinus dalatensis. Part 1. Terpenoids from the leaves

Seven terpenoids were isolated from the dried leaves of Pinus dalatensis Ferre, including one caryolane sesquiterpenoid ( 1 ), five labdane diterpenoids ( 2 , 3 , 4 , 5 , 6 ) and one serratane triterpenoid (7). The structures of the isolated compounds were determined on the basic of spectroscopic methods (ESI-MS, NMR) and comparison with reported data. Among these compounds, the mixture of compounds 2 and 3 showed inhibitory effects on the growth of acute myeloid leukemia (OCI-AML) cells. This is the first report on the chemical compositions of Pinus dalatensis in Vietnam. Keywords. Pinus dalatensis , serratane triterpenoid, caryolane sesquiterpenoid, labdane diterpenoid, acute myeloid leukemia, antiproliferative effect.

Chemical constituents of Chirita drakei Burtt collected in Ha Long Bay, Quang Ninh province, Viet Nam. Part 2. Compounds isolated from the n-butanol extract

Four phenol glycosides together with cannabiside B were isolated from the n-butanol extract of the aerial part of Chirita drakei Burtt collected in islands, on mountain slopes of Ha Long bay, Quang Ninh province. Their structures have been elucidated by mass, NMR spectroscopy and comparison with published data. Compounds 4 and 5 were obtained for the first time from the genera Chirita.

Chemical constituents of Oldenlandia pinifolia and their antiproliferative activities

Abstract This study describes the chemical constituents of Oldenlandia pinifolia (Wall. Ex G. Don) Kuntze (synonym Hedyotis pinifolia Wall. Ex G. Don) and discusses their anti-proliferative activities. Thirteen compounds were isolated from the n-hexane, ethyl acetate and n-butanol extracts of whole plants O. pinifolia by chromatography method. Their structures were elucidated using MS and NMR analysis and compared with reported data. They are three anthraquinones, a carotenoid, two triterpenes, four iridoid glycosides and three flavonoid glycosides. Among them, 2-methyl-1,4,6-trihydroxy-anthraquinone is a new one, and three compounds were found for the first time in this genus. MTT assay resulted that the n-butanol extract and four isolated compounds inhibited the proliferation of chronic myelogenous leukaemia cells. The results from Hoechst 33343 staining and caspase 3-inducing exhibited that those four tested compounds induced apoptosis and activated caspase 3 (p < 0.05). One of them, isorhamnetin-3-O-β-rutinoside showed the most activity with IC50 value of 394.68 ± 25.12 μM.

Diterpenoids from the wood of Podocarpus neriifolitus

Using combined chromatographic methods, three known diterpenoids, inumakiol D ( 1 ), totarol ( 2 ) and totarol-19-carboxylic acid ( 3 ) along with β -sitosterol and β -sitosterol glucoside were isolated from the ethyl acetate extract of the wood of Podocarpus neriifolius collected in Lam Dong province, Vietnam. Their structures were determined by MS, 1D-, 2D-NMR data analysis and comparison with published references. This is the first report of compounds 1-3 from this plant. Keywords. Podocarpus neriifolius, diterpenoid, inumakiol D, totarol, totarol-19-carboxylic.

SYNTHESIS AND CYTOTOXIC ACTIVITY OF DERIVATIVES OF 24-NOR-LUPANE-TRITERPENOID ACIDS ISOLATED FROM Acanthopanax trifoliatus

Starting from 24-nor-11α-hydroxy-3-oxo-lup-20(29)-en-28-oic acid (1) and 24-nor-3α,11α-dihydroxy-lup-20(29)-en-28-oic acid (2), isolated from the aerial parts of Acanthopanax trifoliatus (Araliaceae), 19 new derivatives have been synthesized. Their structures were confirmed by IR, MS, and NMR spectral data. Some of the synthesized compounds have been selected for cytotoxicity test on four human cancer cell lines, including KB, HepG2, MCF7, and Lu. Among these, compounds 6, 7, 8, and 18 showed stronger cytotoxicity than the parent compounds; in particular, compound 18 is 6–15 times more active than its lead compound on all four tested cell lines.