Synthesis and biological evaluation of cinnamyl compounds as potent antitumor agents

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 19, 2007, Pages 5423-5427

  Shin, Dae Seop ^a,b   Kim, Jiin ^a   Han, Dong Cho ^a   Son, Kwang Hee ^a   Lee, Chang Woo ^a   Kim, Hwan Mook ^a   Hong, Su Hyung ^c   Kwon, Byoung Mog ^a,b  

^a Korea Research Institute of Bioscience and Biotechnology (KRIBB)   (South Korea)

^b University of Science and Technology (UST)   (South Korea)

^c Kyungpook National University   (South Korea)

Author keywords

Apoptosis; Cell cycle; Cinnamaldehyde

Indexed keywords

ANTINEOPLASTIC AGENT; CINNAMALDEHYDE DERIVATIVE; HYDROXYLAMINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CANCER INHIBITION; COLORECTAL CARCINOMA; CONTROLLED STUDY; DRUG SCREENING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; NUDE MOUSE; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CASPASE 3; CELL CYCLE; CELL DIVISION; CELL LINE, TUMOR; CINNAMATES; CINNAMOMUM; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; G2 PHASE; HUMANS; MICE; MICE, NUDE; NEOPLASM TRANSPLANTATION; POLY(ADP-RIBOSE) POLYMERASES;

MUS MUSCULUS;

EID: 34548546377     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.07.033     Document Type: Article

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16. 3/TMS) (ppm); δ 3.52 (broad, 4H), 3.70 (t, 4H, J = 4.8 Hz), 6.47 (d. 1H, J = 15.9 Hz), 7.22-7.68 (m, 7H), 7.88 (d, 1H, J = 15.9 Hz), 8.20 (d, 2H, J = 7.5 Hz), 9.16 (broad, 1H).
17. Growth inhibitory assay. Cells were seeded at a density of 5000 cells/well in a 96-well microtiter plate. Cells were counted with a hemocytometer. After 24 h, cells were replenished with fresh complete medium containing compounds or 0.1% DMSO. After incubation for 48 h, cell proliferation reagent WST-1 (Roche) was added to each well. The amount of WST-1-formazan produced was measured at 450 nm by ELISA Reader (Bio-Rad).
18. 5 cells) and treated with 100 μg/mL of RNase A at 37 °C for 30 min. Propidium iodide was then added to a final concentration of 50 μg/mL for DNA staining and 20,000 fixed cells were analyzed on a FACScalibur (Becton-Dickinson, San Jose, CA). Cell cycle distribution was analyzed using the Modifit's program (Becton-Dickinson).
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20. SW620 and HCT 116 cells were treated with 10-40 μM of 6 for 24 h and a 20 μg protein isolated from cell lysates was resolved by 15% SDS-PAGE and transferred to the PVDF membrane (Roche, Germany). The membrane was blocked with 5% nonfat dried milk in TBS-T (50 mM Tris-HCl, pH 7.6, 150 mM NaCl, and 0.1% Tween 20). The primary antibodies used were from Cell Signaling. The secondary antibodies used were horseradish peroxidase-conjugated goat anti-rabbit IgG (1:3000) from Jackson immunology. The antibodies were used at dilution recommended by the manufacturers. Membrane was incubated with primary antibody for 2 h at room temperature, washed five times with TBS-T. And the proteins were developed using a chemiluminescence peroxidase reagent (Roche Applied Science) and exposed to X-ray films.
21. 7 cells/mL) were implanted subcutaneously into the right flank of nude mice on day 0. Compounds were dissolved in 0.5% Tween 80 and were intraperitoneously administered at a concentration of 50 mg/kg per day for 20 days. Doxifluridine was used as a reference compound and its dosage was 50 mg/kg. Test substances were administrated in a volume of 0.2 mL per 20 g body weight of animals. On day 14, the mice were sacrificed and tumor volumes were estimated [length (mm) × width (mm) × height (mm)/2]. Animal experiments were performed under the permission according to 'Institutional Guideline of Animal Experiments' of Korea Research Institute of Bioscience & Biotechnology.