Mingchuan Liu

Chemical Constituents of the Ethyl Acetate Extract of Belamcanda chinensis (L.) DC Roots and Their Antitumor Activities

An activity-directed fractionation and purification process was used to isolate antitumor compounds from the roots of Belamcanda chinensis (L.) DC. The ethyl acetate extract showed greater antitumor activities than the other extracts, consequently leading to the isolation of 18 compounds identified as β-sitosterol (1), dausterol (2), quercetin (3), kampferol (4), shikimic acid (5), gallic acid (6), ursolic acid (7), betulin (8), betulonic acid (9), betulone (10), tectoridin (11), irisflorentin (12), 4′,5,6-trihydroxy-7-methoxyisoflavone (13), tectorigenin (14), irilins A (15), iridin (16), irigenin (17), and iristectongenin A (18). Compounds 3–10, 13, and 15 were isolated from B. chinensis for the first time. Compounds 4 and 7–10 showed potent cytotoxic activities against PC3, MGC-803, Bcap-37, and MCF-7 cell lines. The mechanism of the antitumor action of compound 7 was preliminarily investigated through acridine orange/ethidium bromide (AO/EB) staining, Hoechst 33258 staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which indicated the growth inhibition of MGC-803 cells via the induction of tumor cell apoptosis.

Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety

This study designed and synthesized a series of novel ursolic acid derivatives in an attempt to develop potent antitumor agents. Their structures were confirmed using MS, IR, (1)H NMR and (13)C NMR. The inhibitory activities of the title compounds against the MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer cell) human cancer cell lines were evaluated using standard MTT assay in vitro. The pharmacological results showed that some of the compounds displayed moderate to high levels of antitumor activities against the tested cancer cell lines and that most exhibited more potent inhibitory activities compared with ursolic acid. The mechanism of compound 4b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, TUNEL assay and flow cytometry, which revealed that the compound can induce cell apoptosis in MGC-803 cells.

Synthesis and in vitro antitumor evaluation of betulin acid ester derivatives as novel apoptosis inducers

Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines in vitro by MTT assay. Some derivatives (compounds 3a-3d and 5) displayed strong antitumor properties, with IC50 values between 4 and 18 μM. Compound 3c, containing piperidine group at C-28 position, had IC50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 μM on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 μM 3c.

Synthesis and biological evaluation of betulonic acid derivatives as antitumor agents.

Structural modification was performed at the C-28 position of betulonic acid (BetA). Twenty-five BetA derivatives were synthesized, and evaluated for their antitumor activities against MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines by MTT assay. Among the derivatives, most of the derivatives had significant antiproliferative ability (IC50 < 19 μM). Compound 3k, the most active compound, showed IC50 values of 3.6, 5.6, 4.2, 7.8, and 5.2 μM on the five cancer cell lines respectively, and was selected to investigate cell apoptosis by subsequent florescence staining and flow cytometry analysis. The results revealed that compound 3k could induce apoptosis in MGC-803 cell lines, and the apoptosis ratios reached 28.33% after 36 h of treatment at 10 μM. In addition, the study of cancer cell apoptotic signaling pathway indicated that the apoptosis of MGC-803 cells induced by compound 3k could be through the mitochondrial intrinsic pathway.

Discovery and antitumor activities of constituents from Cyrtomium fortumei (J.) Smith rhizomes

BackgroundCyrtomium fortumei (J.) Smith is an important Chinese herbal medicine because of its biological functions. However, systematic and comprehensive studies on the phytochemicals from Cyrtomium fortumei (J.) Smith and their bioactivity are limited.ResultsUsing the bioassay-guided technique, the ethyl acetate and n-BuOH extracts of the rhizomes of Cyrtomium fortumei (J.) Smith were shown to exhibit good antitumor activities, consequently leading to the isolation of 23 compounds. All compounds were isolated from the plant for the first time. The inhibitory activities of these compounds were investigated on tumor cells MGC-803, PC3, and A375 in vitro by MTT (thiazolyl blue tetrazolium bromide) assay, and the results showed that pimpinellin (3) had potent cytotoxic activities against the three cell lines, with the IC50 values of 14.4 ± 0.3 μM, 20.4 ± 0.5 μM, and 29.2 ± 0.6 μM, respectively. The mechanism of the antitumor action indicated that pimpinellin inhibited the growth of MGC-803 cells via the induction of tumor cell apoptosis, with apoptosis ratio of 27.44% after 72 h of treatment at 20 μM.ConclusionsThis study suggests that most of the compounds from the roots of Cyrtomium fortumei (J.) Smith could inhibit the growth of human carcinoma cells. Moreover, pimpinellin inhibited the growth of tumor cells via the induction of tumor cell apoptosis.

Chemical constituents of Cyrtomium fortumei (J.) Smith

Five known compounds, 6′-methylglucuronide-5-hydroxy-chromone (1), ethyl α-d-glactopyranoside (2), neoechinulin A (3), 9,12,13-trihydroxyoctadeca-10(E),15(Z)-dienoic acid (4) and phellopterin (5), were isolated from water extract of Cyrtomium fortumei (J.) Smith. Compounds 1–5 were isolated from this genus for the first time, and all the compounds were evaluated in vitro against a panel of human cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Among them, compounds 3 and 4 exhibited significant cytotoxic activities, with IC50 values of 15.2 and 18.3 μg/mL on MGC-803 cells, respectively.

Synthesis and evaluation as potential antitumor agents of novel ursolic acid derivatives

Novel ursolic acid derivatives were synthesized, and their structures were confirmed by MS, IR, 1H NMR and 13C NMR spectral analysis. In vitro antitumor activities of these compounds against MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer cell) human cancer cell lines were evaluated by MTT assay. The pharmacological screening results revealed that many derivatives exhibited moderate to high activities against the tested cell lines, and that most demonstrated more potent inhibitory activities than that of ursolic acid. Preliminarily mechanism study of representative compound 3h were carried out by acridine orange/ethidium bromide staining, Hoechst 33258 staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, and flow cytometry which indicated that compound 3h can induce cell apoptosis of MGC-803 cells, and the apoptosis ratio reached 34.59 % after 36 h treatment at 10 μM.

Chemical Composition of the Essential Oil from Rhizomes of Cyrtomium fortumei

Table 1 gives data on the composition of the essential oil; 21 compounds were detected. The plant contains a high content of octadecanoic acid (28.32%) and hexadecanoic acid (21.57%); other important components were found to be 2-pentadecanone (9.55%), 18-nonadecenoic acid (6.54%), 2-acetoxytridecane (3.91%), 4,9-dimethoxy-7H-furo[3,2-g]chromen7-one (2.83%), and (Z)-11-hexadecenoic acid (2.73%). Organic acids were the dominant class of compounds, constituting 59.16% of the total oil. However, coumarins and steroids constituted only 3.44% and 4.25% of the total oil, respectively. In this study, the rhizomes of Cyrtomium fortumei were collected from Longli, Guizhou Province in China, in August 2011. Professor Qingde Long, Department of Medicine, Guiyang Medical University, identified the plant material. A voucher specimen was deposited at Guiyang Medical University, Guiyang, China. About 250 g of the dried rhizomes of Cyrtomium fortumei were cut into pieces and submitted to extraction. A CO 2 flow rate of 30 L/h and an extraction period of 60 min were used. The extraction was performed under a pressure of 33 MPa and at a temperature of 42C. The essential oil obtained by supercritical carbon dioxide extraction assay (SFE–CO 2 ) was a yellow viscous oil (yield 1.2%). The oil was dried over anhydrous Na 2 SO 4 and placed at a low temperature in the refrigerator until analysis. The composition of the oil was studied by GC on a Agilent 6890 instrument coupled to a flame ionization detector (FID), using a fused-silica column (30 m 0.25 mm i.d; 0.25 m film thickness) coated with 5% phenylmethylsiloxane (HP-5 capillary column). The column temperature as kept at 50C for 2 min and programmed to 290C at a rate of 5C/min. Injector and detector temperatures were 250C, and the flow rate of helium as carrier gas was 1.0 mL/min. GC/MS data were obtained on a Agilent 5973 mass spectrometer using a HP-5 MS capillary column (5% phenylmethylsiloxane, 30 m 0.25 mm i.d; 0.25 m film thickness). The carrier gas was helium and the chromatographic conditions were as above (ion source temperature 230C; interface temperature 280C; acquisition mass range 10–550 amu; ionization energy 70 eV). The components were identified by comparison of their mass spectra with those of the NIST 5 mass spectral library.

Chemical Constituents of Thalictrum ichangense

Thalictrum ichangense Lecoyer. ex Oliv. belongs to the Ranunculaceae family and is a perennial herbaceous plant distributed widely in the North Temperate Zone [1]. In the past, Thalictrum ichangense was used for the treatment of various diseases, such as cancer, hypertension, hepaatitis, diuresis, heart disorders, and inflammation [2]. However, the constituents of the plant remain unclear. Thus, it is necessary to clarify the chemical composition of this plant. We have recently investigated the chemical constituents of Thalictrum ichangense roots systematically. The roots of Thalictrum ichangense were collected in Longli, Guizhou Province, China, in May, 2011. The plant was identified by Prof. Qingde Long, Department of Medicine, Guiyang Medical University. A voucher specimen is deposited at Guiyang Medical University, Guiyang, China. Air-dried and powdered roots of Thalictrum ichangense (20 kg) were extracted with 80% EtOH (3 20 L) under reflux for 8 h. Evaporation of the solvent yielded an extract (212 g), which was suspended in water and partitioned with petroleum ether, EtOAc, and n-BuOH. The EtOAc extract (97 g) was subjected to a series of chromatographic techniques, such as column chromatography using silica gel (mesh 200–300) and Sephadex LH-20, yielding compounds 1–10. The structures of these compounds were elucidated by a combination of 1H, 13C NMR, and ESI spectral analysis and from their physicochemical properties, and were identified as -sitosterol (1) [3], daucosterol (2) [4], hexacosanoic acid methyl ester (3) [5], genkwanin (4) [6], 9,10,13-trihydroxy-(E)-11-octadecenoic acid (5) [7], linarin (6) [8], palmitic acid ester of coniferyl alcohol (7) [9], columbin (8) [10], primulagenin A (9) [11], and heneicosanol (10) [12]. All the compounds were obtained from this plant for the first time. -Sitosterol (1). White needles; mp 141–143 C. EI-MS m/z 414 [M]+; C29H50O. Daucosterol (2). White powder; mp 290–293 C. EI-MS m/z 576 [M]+; C35H60O6. 1H NMR (500 MHz, C5D5N, ppm, , J/Hz): 5.30 (1H, s, H-6), 4.36 (1H, dd, J = 5.3, 5, H-3), 4.24 (1H, t, J = 8.9, H-1 ). 13C NMR (125 MHz, C5D5N, , ppm): 140.75 (C-5), 121.7 (C-6), 102.43 (C-1 ), 78.48 (C-5 ), 77.92 (C-3 ), 75.21 (C-2 ), 71.54 (C-4 ), 62.68 (C-6 ), 56.67 (C-14), 56.08 (C-17), 50.19 (C-9), 45.88 (C-24), 42.33 (C-16), 39.79 (C-13), 39.19 (C-4), 37.33 (C-1), 36.78 (C-23), 36.24 (C-20), 34.05 (C-22), 32.03 (C-7), 31.89 (C-8), 30.11 (C-2), 29.30 (C-25), 28.39 (C-12), 26.22 (C-10), 24.36 (C-15), 23.23 (C-28), 21.14 (C-11), 19.83 (C-27), 19.28 (C-19), 19.06 (C-21), 18.86 (C-26), 12.01 (C-29), 11.83 (C-18). Hexacosanoic Acid Methyl Ester (3). White amorphous powder; mp 73–75 C. EI-MS m/z 410 [M]+; C27H54O2. 1H NMR (500 MHz, CD3OD, ppm, , J/Hz): 4.88 (3H, s, CH3), 2.24 (2H, t, J = 8.3, CH2), 1.54 (2H, m, CH2), 1.20–1.30 (44H, m, CH2), 0.87 (3H, t, J = 9.2, CH3). 13C NMR (125 MHz, CD3OD, , ppm): 176.40 (C-2), 33.62 (C-3), 31.76 (C-25), 29.46 (C-9, 23), 29.40 (C-24), 29.30 (C-5), 29.17 (C-6), 29.12 (C-7), 28.93 (C-8), 24.78 (C-4), 22.42 (C-26), 13.12 (C-1, 27). Genkwanin (4). Light yellow powder; mp 282–284 C. EI-MS m/z 284 [M]+; C16H12O5. 1H NMR (500 MHz, CD3OD, ppm, , J/Hz): 12.90 (1H, s, 5-OH), 10.86 (1H, s, 4 -OH), 7.99 (2H, d, J = 4.2, H-2 , 6 ), 7.07 (2H, d, J = 10, H-3 , 5 ), 6.85 (1H, s, H-3), 6.47 (1H, s, H-8), 6.17 (1H, s, H-6), 3.82 (3H, s, 7-OCH3). 13C NMR (125 MHz, CD3OD, , ppm): 182.23 (C-4), 164.75 (C-7), 163.82 (C-2), 162.84 (C-4 ), 161.97 (C-5), 157.88 (C-9), 104.05 (C-3), 128.88 (C-2 , 6 ), 123.33 (C-1 ), 115.11 (C-3 , 5 ), 104.27 (C-10), 99.42 (C-6), 94.57 (C-8), 56.09 (OCH3).