OBJECTIVE: To prepare Formononetin (FMN) inclusion compound liposome and evaluate its quality. METHODS: FMN inclusion compound liposome was prepared by film dispersion method. The morphology, particle size, Zeta potential, encapsulation efficiency and in vitro release properties were studied. RESULTS: The particle size, Zeta potential and encapsulation efficiency of prepared FMN inclusion compound liposome were (255. 34 ± 12. 87) nm, (25. 32 ± 3. 51) mV, (81. 63 ± 0. 79)％, respectively (n=3). The 24 h accumulative release rate of prepared FMN inclusion compound liposome was 56. 12％. CONCLUSIONS: FMN inclusion compound liposome with good sustained-release effect is prepared successfully and in line with related quality standard.

OBJECTIVETo synthesize compounds based on imidazo-fused heterocycles and evaluate their anti-tumor activity against breast cancer.

METHODSThe compounds 1a-1e, 2a and 2b were synthesized by aerobic copper-catalyzed halocyclization of methyl N-heteroaromatics with aliphatic amines; 3a and 3b were generated by sonogashira reaction and Suzuki reaction, respectively; the compounds 4a-4c were obtained by Buchwald-Hartwig reaction of the corresponding amines and 1e. The effects of these compounds against breast cancer cells and their nephrotoxicity were determined using MTT assay. Annexin VFITC/PI apoptosis detection kit was used to assess the apoptosis-inducing effects of these compounds in breast cancer cells. With normal saline as the control, the safety and anti-tumor activity of the compound 2a (daily dose of 10 mg/kg for 14 days) was tested in a mouse model bearing human breast cancer xenografts.

RESULTSThe compounds 2a, 4a, 4b and 4c all showed obvious anti-tumor activities. Among these compounds, 2a showed the most potent anti-tumor effect against breast cancer cells with an IC of 9.77 ± 2.32 μmol/L, similar to that of cisplatin (IC=8.96 ± 2.35 μmol/L); 2a also showed a slightly lower nephrotoxicity than cisplatin, and their CC was 10.79±0.87 μmol/L and 8.45±0.68 μmol/L, respectively. 2a obviously promoted apoptosis of breast cancer cells and caused a moderate suppression of the breast cancer growth in the tumor-bearing mouse models without producing serious adverse effects.

CONCLUSIONSFour compounds synthesized based on imidazo-fused heterocycles have anti-tumor activities against breast cancer. The compound 2a is capable of dose-dependently promoting apoptosis of breast cancer cells and has a good safety and a moderate efficacy for suppressing tumor growth in mouse models bearing human breast cancer xenografts.