A pH-sensitive prodrug strategy to co-deliver DOX and TOS in TPGS nanomicelles for tumor therapy.

This work has presented a novel strategy for designing pH-sensitive TOS-H-DOX prodrug-loaded TPGS nanomicelles for co-delivery TOS and DOX to enhance tumor therapy and reduce the toxic side effects. DOX was covalently conjugated to the vitamin E succinate through hydrazone bond to produce an pH-sensitive prodrug TOS-H-DOX (amido bond as a control, TOS-A-DOX), which was responsive to the acidic environment in tumor cells, and the prodrugs were subsequently encapsulated in the core of TPGS nanomicelles via hydrophobic effects with a significant drug loading capacity. The pH-sensitive prodrug nanomicelles TOS-H-DOX/TPGS exhibited potent release of DOX in acidic media relative to the pH-insensitive prodrug nanomicelles TOS-A-DOX/TPGS, and further studies of their intracellular uptake and intracellular localization demonstrated that TOS-H-DOX/TPGS nanomicelles can be effectively taken up by cells and drugs can be released. In vitro results confirmed that TOS-H-DOX/TPGS nanomicelles exhibited significant antitumor cell proliferation activity compared to TOS-A-DOX/TPGS and free DOX, TPGS. Furthermore, in vivo studies further confirmed an excellent synergistic antitumor efficacy in MCF-7 tumor-bearing nude mice model. More importantly, the H&E staining of the heart, liver, kidney tissue sections of experimental nude mice showed that TOS-H-DOX/TPGS nanomicelles can reduce damage to them.

Design, synthesis and biological evaluation of 3',4',5'-trimethoxy flavonoid benzimidazole derivatives as potential anti-tumor agents.

A series of 3',4',5'-trimethoxy flavonoids with benzimidazole linked by different chain alkanes have been designed and synthesized. The potential activity of these compounds as anti-tumor agents was evaluated by cytotoxicity assay in MGC-803 (human gastric cancer), MCF-7 (human breast cancer), HepG-2 (human hepatoma) and MFC (mouse gastric cancer) tumor cell lines. Among them, compound 15 7-(3-(2-chloro-1H-benzo[d]imidazol-1-yl)propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one displayed the most potent antiproliferative activity, with IC50 values of 20.47 ± 2.07, 43.42 ± 3.56, 35.45 ± 2.03 µM and 23.47 ± 3.59 µM, respectively. The flow cytometry (FCM) results showed that compound 15 caused the cell cycle to be arrested in G1 phase and induced apoptosis of MFC cells in a dose-dependent manner. In addition, compound 15 exhibited a significant inhibitory effect on tumor growth in vivo. All the results outlined the great potential of compound 15 for further exploitation as anti-tumor agent.

Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin salicylate derivatives.

A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-803cells and MFC cells. Among them, compound 3f showed the most potent activity against MGC-803 cells and MFC cells with IC50 values of 23.83 ± 3.68 and 27.34 ± 5.21 µM, respectively. The flow cytometry assay reconfirmed that compound 3f promoted the occurrence of tumour cells' G1/S block under the inhibiting effect of compound 3f. Compound 3f possessed higher antitumour efficacy in tumour-bearing mice, compared with the positive control 5-Fu and the blank control saline.

Design, synthesis and biological evaluation of chrysin benzimidazole derivatives as potential anticancer agents.

A series of chrysin benzimidazole derivatives were synthesised and evaluated for their anticancer activity in the search for potential anticancer agents. Among them, compound 18 displayed the most potent anti-proliferative activity against MFC cells with IC50 values of 25.72 ± 3.95 µM. The flow cytometry results displayed that compound 18 induced apoptosis of MFC cells in a dose-dependent manner and caused the cell cycle to be arrested in the G0/G1 phase. Furthermore, the preliminary anticancer activity in vivo was also studied in tumour-bearing mice, and the compound 18 exerted good inhibition effect on tumour growth. These results suggested that compound 18 had good anticancer activity, which could be a potential anticancer agent after further optimisation and evaluation.