- Synthesis and hypoglycemic activity of 9-O-(lipophilic group substituted) berberine derivatives
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A series of 9-O-(lipophilic group substituted) berberine derivatives were synthesized and evaluated for their cytotoxicity and hypoglycemic activity against HepG2 cells. All the results indicated that most of the synthesized compounds exhibited lower cytotoxicity and a certain degree of hypoglycemic activity. Especially the compounds 5g and 5h displayed dramatically increased hypoglycemic activity compared with berberine, and the cytotoxicity maintained or even lower than berberine, indicating that they are potential candidates for new anti-type 2 diabetes mellitus drugs.
- Zhang, Shanshan,Wang, Xiaohong,Yin, Weicheng,Liu, Zhenbao,Zhou, Mi,Xiao, Daipeng,Liu, Yanfei,Peng, Dongming
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- Synthesis method of berberrubine ester substances
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The invention discloses a synthesis method of berberrubine ester substances. The method comprises the following steps: using 4-dimethylaminopyridine as a catalyst and dicyclohexylcarbodiimide as a deacidifying agent, directly reacting berrubine with carboxylic acid in a certain solvent to generate the berrubine ester substances with bioactivity, reacting for 1.5-2 hours at the temperature of between 40 and 60 DEG C, basically finishing the reaction, filtering to remove solid substances while the reaction is hot, freezing overnight to separate out a target object, filtering, washing, drying andthe like to obtain a yellow crude product, and finally, separating the crude product by using a methanol dichloromethane column with the volume ratio of 1: 10, and further purifying the product to obtain the product. The yield of the product is 85.2%-93.4%, and the purity of the product is greater than 96%. Compared with traditional synthesis of berberrubine ester, the method has the advantages that the reaction yield is high, and the product is good in color and luster and high in purity; the method has the advantages of mild reaction conditions, short reaction time, fewer byproducts, accessible raw materials, simple operation, easy post-treatment and the like.
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Paragraph 0032-0039; 0038-0043; 0085-0089
(2020/12/30)
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- Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine
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In order to enhance oral bioavailability of berberine (BBR) for its cholesterol-lowering efficacy in vivo, a series of ester or ether prodrugs of berberrubine (M1), which is an active metabolite of BBR after first-pass metabolism, were designed, semi-synthesized, and evaluated. Among these M1 prodrugs, compound 5g possessing palmitate at the 9-position showed a moderate Log P value and esterase hydrolysis rate for releasing M1 in blood. Its cholesterol-lowering efficacy in vivo was evaluated in hyperlipidemic SD rats. Compound 5g (100 mg/kg/d) reduced blood CHO and LDL-c by 35.8% and 45.5%, respectively, similar to that by BBR. It also exhibited a good safety in rats with no side-effect on liver and kidney function. Therefore, the design of M1 prodrug appears to be an effective strategy to improve pharmacokinetic feature of BBR for its lipid-lowering efficacy in vivo.
- Li, Ying-Hong,Li, Yi,Yang, Peng,Kong, Wei-Jia,You, Xue-Fu,Ren, Gang,Deng, Hong-Bin,Wang, Yue-Ming,Wang, Yan-Xiang,Jiang, Jian-Dong,Song, Dan-Qing
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experimental part
p. 6422 - 6428
(2010/10/04)
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