Synthesis and Pharmacological Evaluation of Maleopimaric N-arylimides: Identification of Novel Proapoptotic Agents.

Several N-aryl maleopimaric acid diimides (3a-3d, 4a-4g) were synthesized and evaluated their topoisomerase I inhibitory activities along with cytotoxicities against NCI, MGC-803, Bel-7404 and Hct-116 cell lines. The pharmacological dates revealed that most of structure analogs exhibited moderate to high levels of anticancer activities against the tested cancer cell lines. Compound 4g with phenylalanine substituent exhibited significant cytotoxicity against MGC-803 and Hct-116 cells (IC50 was 9.85±1.24 and 8.47±0.95 µM, respectively). All the synthesized compounds exhibited no cytotoxicity against HUVEC cells. In addition, maleopimaric diimides showed stronger cytotoxicity and topoisomerase I inhibitory activity compared to that of maleopimaric acid. Structure-activity relationship study showed that carboxyl and diimide moieties were important to display Topo I inhibitory activities. Further experiments proved that 4g could induce apoptosis of MGC-803 cells. In addition, the further mechanisms of compound 4g-induced apoptosis in MGC-803 cells demonstrated that compound 4g induced the activations of caspase-4, caspase-8 and caspase-3 for causing cell apoptosis, and altered antiand pro-apoptotic proteins. Moreover, cell cycle analysis indicated that the derivative 4g mainly arrested MGC-803 cells in S stage.

Synthesis and antitumor activity evaluation of maleopimaric acid N-aryl imide atropisomers.

Maleopimaric acid N-aryl imides (2) and methyl maleopimaric acid N-aryl imides (3) were designed and synthesized. Their atropisomers (A and B) were separated into their enantiomeric pure forms and the anti-proliferative activity was tested against NCI, A549, Hep G-2, MGC-803 and Hct-116 cell lines, respectively. A significant difference in the level of cytotoxicity was observed between R and S conformers. Atropisomers A with an R configuration exhibited significant toxicity (the IC50 values ranging from 7.51 to 32.1 µM). Further experiments proved that antitumor activity of 2A was achieved through the induction of cell apoptosis by G1 cell-cycle arrest.

[Application value of high-frequency ultrasound on the diagnosis of rotator cuff tears].

OBJECTIVE: To study the diagnostic value of high frequency ultrasound in diagnosing rotator cuff tears. METHODS: Total 37 patients (37 shoulders) with rotator cuff tears were detected by ultrasound, MRI examination and arthroscopy retrospectively. Among the patients,21 patients were male and 16 patients were female. The average age was 64 years old (ranged, 51 to 75 years old). High frequency ultrasonography and MRI were applied to exam the shoulder under the standardizeds to point types and compare with arthroscopy results. RESULTS: Thirty-two shoulders were diagnosed as rotator cuff injury by ultrasound, and 5 shoulders were detected as normal rotator cuff by ultrasound. Twenty-nine shoulders were diagnosed as rotator cuff injury by MRI, and 8 shoulders were detected as normal rotator cuff by MRI. Thirty-three shoulders were diagnosed as rotator cuff injury during the operation, and 4 shoulders were regarded as rotator cuff during the operation. The sensitivity of ultrasound diagnosis was 93.4% (31/33), and specific degree was 75.0%(3/4). The sensitivity of MRI diagnosis was 87.5% (28/32), and specific degree was 80.0% (4/5). CONCLUSION: High frequency ultrasound in the diagnosis of rotator cuff tears injuries has a high sensitivity and specificity. High frequency ultrasound can be used as a routine method to diagnose rotator cuff tears injuries.