Zhu-Bo Li

N-Benzyl-2-(2,4-dichloro­phen­oxy)acetamide

In the title compound, C15H13Cl2NO2, the dihedral angle between the aromatic rings is 27.17 (11)°. In the crystal the molecules are linked by N—H⋯O hydrogen bonds.

N-Benzyl-2-(2-chloro-4-methyl-phen-oxy)acetamide.

The structure determination of the title compound, C16H16ClNO2, was performed as part of a project on the interactions between small organic molecules and proteins. In the crystal structure, the dihedral angle between the two aromatic rings is 16.14 (12)°. The molecules are connected via N—H⋯O hydrogen bonding into chains, which extend in the direction of the b axis.

Absorption properties and effects of caffeic acid phenethyl ester and its p-nitro-derivative on P-glycoprotein in Caco-2 cells and rats

Abstract Context: Caffeic acid phenethyl ester (CAPE), isolated from honeybee propolis, has pharmacological applications. A synthesized CAPE derivative, p-nitro-caffeic acid phenethyl ester (CAPE-NO2), showed similar activities with CAPE. The pharmacological activities of CAPE and CAPE-NO2 are related to their absorption properties. Objective: To understand the pharmacokinetic profiles of CAPE and CAPE-NO2 in rats and investigate the absorption mechanisms and effects on P-glycoprotein in Caco-2 cells. Materials and methods: The pharmacokinetic profiles of CAPE and CAPE-NO2 were obtained after oral administration (10 mg/kg) to rats. Transport studies of CAPE and CAPE-NO2 (5, 10, 20 μM) were performed in Caco-2 cell model. P-gp activities were assayed by rhodamine 123 cellular retention. Expression of P-gp was determined after the cells were administrated with CAPE and CAPE-NO2 (5, 20 μM) for 48 and 72 h. Results: The AUC(0−t) of CAPE-NO2 (3239.9 ± 352 ng × h/mL) was two-time greater than CAPE (1659.6 ± 152 ng × h/mL) in rats. The Papp values of CAPE and CAPE-NO2 were (4.86 ± 0.90) × 10−6 cm/s and (12.34 ± 1.6) × 10−6 cm/s, respectively. The accumulation of rhodamine 123 was increased by 1.3- to 1.9-fold and 1.4- to 2.3-fold in CAPE and CAPE-NO2 groups after 1 h administration, respectively. However, CAPE and CAPE-NO2 increased the P-gp levels by 2.1- and 1.7-fold, respectively. Conclusion: The absorption of CAPE-NO2 can be enhanced in rats and Caco-2 cells compared with CAPE. The two compounds are potential inhibitors of P-gp. The increased P-gp levels generated by CAPE and CAPE-NO2 played a role as a defense mechanism by limiting intracellular xenobiotic levels.

Anti-colon cancer effect of caffeic acid p -nitro-phenethyl ester in vitro and in vivo and detection of its metabolites

Caffeic acid phenethyl ester (CAPE), extracted from propolis, was proven to inhibit colon cancer. Caffeic acid p-nitro-phenethyl ester (CAPE-pNO2), a derivative of CAPE, was determined to be an anti-platelet agent and a protector of myocardial ischaemia with more potent effects. In the present study, CAPE-pNO2 showed stronger cytotoxic activity than CAPE. We revealed interactions between CAPE-pNO2 and experimental cells. CAPE-pNO2 induced apoptosis in HT-29 cells by up-regulating P53, cleaved-caspase-3, Bax, P38 and CytoC; CAPE-pNO2 also up-regulated P21Cip1 and P27Kip1 and down-regulated CDK2 and c-Myc to promote cell cycle arrest in G0/G1. In xenograft studies, CAPE-pNO2 remarkably suppressed tumour growth dose dependently and decreased the expression of VEGF (vascular endothelial growth factor) in tumour tissue. Moreover, HE staining showed that no observable toxicity was found in the heart, liver, kidney and spleen. In addition, metabolites of CAPE-pNO2 in HT-29 cells and organs were detected. In conclusion, para-nitro may enhance the anticancer effect of CAPE by inhibiting colon cancer cell viability, inducing apoptosis and cell cycle arrest via the P53 pathway and inhibiting tumour growth and reducing tumour invasion by decreasing the expression of VEGF; additionally, metabolites of CAPE-pNO2 showed differences in cells and organs.

Inhibited effects of CAPE- p NO 2 on cervical carcinoma in vivo and in vitro and its detected metabolites

The development of advanced cervical cancer therapies is a particularly urgent need due to the strong side effects and toxicities of current treatments. Caffeic acid phenethyl ester (CAPE) exhibits broad-spectrum antitumor activities and little toxicity or side effects. In our previous study, caffeic acid para-nitro phenethyl ester (CAPE-pNO2) significantly improved the effect of anti-platelet aggregation and attenuated myocardial ischemia. Based on this finding, we aimed to further explore the antitumor activity of CAPE-pNO2 in cervical cancer cells and tumor xenografts. In addition, we assessed the biotransformation of CAPE-pNO2 in cervical cancer cells. Our study demonstrated that both CAPE and CAPE-pNO2 can inhibit cell proliferation via the induction of G2/M cell cycle arrest. More importantly, CAPE-pNO2 dramatically induced cell apoptosis via significant down-regulation of pro-caspase-3, pro-caspase-9, Bcl-2, Cyclin B1 and Cdc2 and up-regulation of cleaved-caspase-3, Bax, CytoC and P21Cip1. Moreover, CAPE and CAPE-pNO2 significantly suppressed the growth and angiogenesis of nude mice xenografts. CAPE and CAPE-pNO2 were found to degrade into four and six metabolites, respectively. The metabolites of CAPE and CAPE-pNO2 were different, and the major metabolic pathway may be phase II reactions. These results suggest that CAPE-pNO2 induced cell apoptosis and cell cycle arrest via a strong regulatory effect on relevant apoptotic proteins. Therefore, CAPE-pNO2 should be further studied as a potent anti-cancer agent.

Microwave-assisted synthesis of optically active N -substituted 2-methyl-2 H -benzo[ b ][1,4]oxazin-3(4 H )-ones and -thiazin-3(4 H )-ones via Smiles rearrangement

Correspondence: Dong-Soo Shin Departments of Chemistry and Physics, Changwon National University, 9, Sarim-dong, Changwon, GN, 641-773, South Korea Abstract: Optically active N-substituted-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-ones and N-substituted-2-methyl-2H-benzo[b][1,4]thiazin-3(4H)-ones with potential synthetic and pharmacological interest were prepared via Smiles rearrangement using microwave irradiation in one-pot from inexpensive (S)-2-chloropropionic acid.

4-Benzyl-7-chloro-2H-1,4-benz-oxazin-3(4H)-one.

In the title compound, C15H12ClNO2, the two benzene rings are nearly perpendicular to each other [dihedral angle = 89.99 (13)°]. The O atom of the six-membered heterocyclic ring is disordered over two sites in a ratio of 0.46 (4):0.54 (4) and is displaced from the mean plane formed by other five atoms, resulting an envelope conformation of the six-membered hetercycle ring.

N-Cyclo­hexyl-2-(2,3-dichloro­phenyl­sulfan­yl)acetamide

In the crystal structure of title compound, C14H17Cl2NOS, the cyclohexyl ring has a chair conformation and connects with an equatorial N atom. Molecules are connected via N—H⋯O hydrogen bonds into chains.

8-Chloro-4-cyclo-hexyl-2H-1,4-benzoxazin-3(4H)-one.

In the crystal structure of title compound, C14H16ClNO2, the cyclohexyl ring is in a chair conformation. The molecules are connected into centrosymmetric dimers via weak C—H⋯O hydrogen bonds.

N-Cyclo­hexyl-2-(2,3-dichloro­phen­oxy)acetamide

In the crystal structure of title compound, C14H17Cl2NO2, the cyclohexyl ring is in a chair conformation and the molecules are connected via N—H⋯O hydrogen bonding into chains.