Novel bone cement based on calcium phosphate composited CNT curcumin with improved strength and antitumor properties.

In this study, carboxylated carbon nanotube (CNT)-loaded curcumin (CUR) was blended into calcium phosphate cement (CPC) owing to the poor mechanical properties and single function of CPC as a bone-filling material, and CNT-CUR-CPC with improved strength and antitumor properties was obtained. The failure strength, hydrophilicity, in vitro bioactivity, bacteriostatic activity, antitumor activity, and cell safety of CNT-CUR-CPC were evaluated. The experimental results indicated that the failure strength of CNT-CUR-CPC increased from 25.05 to 45.05 MPa (p < 0.001) and its contact angle decreased from 20.37° to 15.27° (p < 0.001) after the CNT-CUR complex was added into CPC at the rate of 5 wt% and blended. Following soaking in simulated body fluid (m-SBF), the main components of CNT-CUR-CPC were hydroxyapatite (HA) and carbonate hydroxyapatite (HCA). The incorporation of CNT-CUR was beneficial for the deposition of PO43- and CO32-, and it promoted the crystallization of HA and HCA. For CNT-CUR-CPC, the inhibition zone diameter on Staphylococcus aureus was 10.2 ± 1.02 mm (p < 0.001) and it exhibited moderate sensitivity, whereas the inhibition zone diameter on Escherichia coli was 8.3 ± 0.23 mm (p < 0.001) and it exhibited low sensitivity. When compared with the CPC, the cell proliferation rate (RGR %) of the CNT-CUR-CPC decreased by 7.73% (p > 0.05) at 24 h, 17.89% (p < 0.05) at 48 h, and 24.43% (p < 0.001) at 72 h when MG63 cells were cultured on it. In particular, after the MG63 cells were cultured with the CNT-CUR-CPC for 48 h, the number of newly proliferating MG63 cells was significantly reduced, and their growth and adhesion on the surface of the CNT-CUR-CPC were inhibited when compared with the CPC. When 3T3-E1 cells were exposed to the m-SBF immersion solution of CNT-CUR-CPC, the cell proliferation rate (RGR %) was ≥80% (p > 0.05) and the cytotoxicity grade was 0-1. The 3T3-E1 cells were cultured with the m-SBF soaking solution of CNT-CUR-CPC for 24 h, and no significant changes in cell morphology or cytotoxicity were observed. After the 3T3-E1 cells were cultured on CNT-CUR-CPC for 48 h, they could stick to and grow on its surface without adverse reactions. CNT-CUR-CPC had a hemolysis rate of 4.3% (p > 0.05) and did not result in hemolysis and hemagglutination. The obtained CNT-CUR-CPC scaffold material exhibited effective antibacterial activity and cell safety, and could achieve a certain antitumor effect, which has a wide application potential in bone tissue engineering.

Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: synthesis, SAR analysis, and biological activity.

A series of nitrogen-containing flavonoid analogues were designed and synthesized by Mannich reaction, and screened for the inhibitory activities of cyclin-dependent kinases using a FRET-based biochemical assay method. The results showed that C-8 nitrogen-containing baicalein analogues 3a-3f exhibited potent CDK1/Cyclin B inhibitory activities. 5,6,7-Trihydroxy-8-(dimethylaminomethyl)-2-phenyl-4H-chromen-4-one 3a, 5,6,7-trihydroxy-8-(pyrrolid inylmethyl)-2-phenyl-4H-chromen-4-one 3b, and 5,6,7-trihydroxy-8-(piperidinylmethyl)-2-phenyl-4H-chromen-4-one 3c (IC(50) 1.05-1.28 microM) were about sixfold more potent than baicalein 2 (IC(50) 6.53 microM). 5,6,7-Trihydroxy-8-(morpholinomethyl)-2-phenyl-4H-chromen-4-one 3d, 5,6,7-trihydroxy-8-(thiomorpholinomethy)-2-phenyl-4H-chrom en-4-one 3e, and 5,6,7-trihydroxy-8-(4-methylpiperazinylmethyl)-2-phenyl-4H-chromen-4-one 3f (IC(50) 0.27-0.38 microM) were about 20-fold more potent than baicalein, and were at the same level as flavopiridol (IC(50) 0.33 microM).