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OBJECTIVE: To explore the efficient and economical synthesis method of asymmetric monocarbonyl curcumin ana-logues(AMCACs), design and sgnthesize a series of B19(1E, 4E)-1, 5-bis(2,3-dimethoxyphenyl) penta-1, 4-dien-3-one analogs to in- vestigate their anti-gastric cancer activities in vitro. METHODS: A series of asymmetric B19 analogues containing 2, 3-dimethoxyphenyl were designed via the combination principle of medicinal chemistry, and obtained a method for synthesizing intermediate (E)-2-(2, 3- dimethoxybenzylidene) cyclopentanone by one step catalyzed by L-proline. The targeted compounds were screened by MTT as-say, and colony cloning experiments were used to further verify its anti-gastric cancer activity in vitro. RESULTS: Ten novel target compounds were synthesized, and the structures were confirmed by LC-MS and 1H-NMR spectral analysis Among them, compound 6e had the highest inhibitory activity on the growth of gastric cancer cells SGC-7901 and BGC-823, whose IC50 were 9.80 and 13.50 μmol• L 1, respectively. CONCLUSION: L-proline could be used as a catalyst to synthesize asymmetric monocarbonyl curcumin analogues efficiently and economically Compound 6e could effectively inhibit the growth of gastric cancer cells in vitro, and its toxicity and inhibition mechanism of tumor cell growth need to be further studied.
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Objective To investigate the influence of curcumin and its analogue H8 on glucose and lipid metabolism disorder in db/db mice. Methods The type 2 diabetes mouse model (db/db mice) was intragastrically administrated with curcumin and analogue H8 for 8 weeks.The blood biochemical indexes were measured.The expression of PEPCK and G6Pase mRNA was detected by real-time PCR in liver tissues.The expression of PEPCK and G6Pase protein was detected by Western blotting. Results Curcumin analogue H8 reduced blood glucose and lipids in db/db mice (P<0.01) and improved liver function related enzymes significantly.The levels of PEPCK and G6Pase mRNA in db/db mice were significantly decreased (P<0.01) and the expression levels of PEPCK and G6Pase protein were significantly decreased(P<0.01). Conclusion Curcumin analogue H8 improves the glucose and lipid metabolism disorder in db/db mice,and it is related to inhibiting the expression of PEPCK and G6Pase gene and protein.
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AIM:To investigate the protective effect of curcumin analogue L 6H4 on diaphragm of type 2 dia-betic rats.METHODS: SPF male Sprague-Dawley rats ( n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM +L6H4 treatment (DT) group.The rats in the later 4 groups were fed with high-fat diet.After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks.Blood glucose and blood lipid levels were detected biochemically .Fasting serum insulin ( FINS ) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated.Serum adiponectin (APN) level was measured by ELISA.The morphological changes of the diaphragm were observed under light and transmission electron microscopes .Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining . The content of malondialdehyde ( MDA) and the activity of superoxide dismutase ( SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method , respectively .The protein expression of adiponectin receptor 1 ( AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot .RESULTS:The levels of blood lipids , blood glucose , FINS and HOMA-IR in HF and DM groups were higher than those in NC group , but decreased after L6H4 treatment.The serum APN level in HF and DM groups was lower than that in NC group , but increased after treat-ment with L6H4.The muscle fibers of the diaphragm were shrunk , fat particles accumulated in the muscle fibers , and the mitochondria were slightly swollen in HF and DM groups .The diaphragmatic fibrosis was obvious in DM group .These le-sions were relieved after L6H4 treatment.Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups , but decreased after treatment with L 6H4.The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group , but increased after L6H4 treatment. CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats.The strengthened protein expression of AdipoR 1, the increased serum level of APN , and anti-lipid peroxidation may be involved in the process .
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AIM:To investigate the protective effect of curcumin analogue L 6H4 on diaphragm of type 2 dia-betic rats.METHODS: SPF male Sprague-Dawley rats ( n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM +L6H4 treatment (DT) group.The rats in the later 4 groups were fed with high-fat diet.After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks.Blood glucose and blood lipid levels were detected biochemically .Fasting serum insulin ( FINS ) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated.Serum adiponectin (APN) level was measured by ELISA.The morphological changes of the diaphragm were observed under light and transmission electron microscopes .Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining . The content of malondialdehyde ( MDA) and the activity of superoxide dismutase ( SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method , respectively .The protein expression of adiponectin receptor 1 ( AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot .RESULTS:The levels of blood lipids , blood glucose , FINS and HOMA-IR in HF and DM groups were higher than those in NC group , but decreased after L6H4 treatment.The serum APN level in HF and DM groups was lower than that in NC group , but increased after treat-ment with L6H4.The muscle fibers of the diaphragm were shrunk , fat particles accumulated in the muscle fibers , and the mitochondria were slightly swollen in HF and DM groups .The diaphragmatic fibrosis was obvious in DM group .These le-sions were relieved after L6H4 treatment.Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups , but decreased after treatment with L 6H4.The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group , but increased after L6H4 treatment. CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats.The strengthened protein expression of AdipoR 1, the increased serum level of APN , and anti-lipid peroxidation may be involved in the process .
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Objective: To search for the small molecule inhibitor with anti-tumor activity by fibroblast growth factor receptor 1 (FGFR1) as target. Methods: The analogue B6 of EF24 was obtained by reforming mono carbonyl curcumin analogues and applied to identifying the target with FGFR1 kinase activity assay. The effect of EF24 and its analogue B6 on the proliferation of HL7702 in normal human and four tumor cells, such as NCI-H460, SGC-7901, A549, and U251; With the concentration of 2.5, 5, and 10 μmol/L, B6 was used to investigate the phosphorylation inhibition of bFGF/FGFR downstream signal protein expression in NCI-H460 cells and Caspase-3 factor expression. Results: With the FGFR1 as target, B6 could inhibit the phosphorylation of FGFR1 in NCI-H460 cells, AKT, and ERK1/2; It also could inhibit the proliferation of cancer cells and promote cell apoptosis. Conclusion: The analogue B6 of EF24 is obtained from the leading compound EF24 with in vitro anti-tumor effect, which provides the basis of looking for the candidate anti-tumor drugs of FGFR1 inhibitor.
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Objective: A series of mono-carbonyl curcumin analogues containing nitrogen heterocyclic ring were designed and synthesized and their anti-inflammatory activities were detected. Methods: A mixture of thiophen-2-acryloyl chloride and compounds containing nitrogen heterocyclic ring reacted to yield the target compounds, and the structures were identified using 1H-NMR and ESI-MS. The anti-inflammatory activity of these compounds was detected by mouse macrophages producing pro-inflammatory cytokines TNF-α and IL-6 induced by LPS. Results: Thirteen target compounds were synthesized, and some of these compounds could significantly inhibit the production of inflammatory cytokines, especially compound Z5 exhibited the most inhibitory activity. Conclusion: Compounds Z1, Z5, and Z9-Z13 are new compounds, and compound Z5 could be used as the candidate of anti-inflammatory drug.