1095271-65-0

Upstream product

• 15401-69-1 berberrubine chloride 
• 633-65-8 berberine chloride 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives to reduce SREBPs expression for the treatment of hyperlipidemia

Statins play an important role in the treatment of hyperlipidemia, but drug resistance and adverse effects greatly limits their application. To discover new lipid-lowering drugs, three different series of tetrahydroprotoberberine derivatives (THPBs) were designed and synthesized. These compounds were first tested for their effects on viability of HepG2 cells and 21 compounds with the percent of cell viability over 90% were further screened to evaluate their ability to reduce total cholesterol (TC) and triglyceride (TG) levels. Among these derivatives, two compounds displayed significant down-regulation both intracellular of TC and TG content, especially compound 49 exhibited the greatest efficacy. Mechanistically, compound 49 promoted proteasomal degradation of SREBPs. Importantly, compound 49 displayed superior bioavailability (F = 65.1%) and obvious efficacy in the treatment of high fat diet induced obesity in vivo. Therefore, compound 49 is a promising candidate to develop new treatment of hyperlipidemia.

Discovery and structural optimization of 9-O-phenylsulfonyl-berberines as new lipid-lowering agents

Berberine is a quaternary isoquinoline alkaloid that exhibits potent hypoglycemic and hypolipidemic activity. Many medicinal chemists are currently working on structural modifications around the parent scaffold of berberine, expecting to further enhance its hypolipidemic activity and reducing its cytotoxicity. In this study, a focused berberine-like compound library containing 12,600 molecules was built via the introduction of various “drug-like” fragments at the C8 and C9 positions of berberine. Sixteen comopounds were hit by using the in-house QSAR models previously reported by our group. Considering synthesis feasibility and the cost of building-blocks, only four berberine analogs (library ID: 2028, 3847, 6033, and 12456) were selected and synthesized for investigating their lipid-lowering activities. Preliminary lipid-lowering study showed that compound 12456 with the phenylsulfonyl group at the C9 position had potent cholesterol inhibitory activity in HepG2 cells, superior to that of the parent compound berberine. Subsequently, a total of twenty-five 9-O-phenylsulfonyl-berberines (1a-1y) and twenty-four 9-O-phenylsulfonyl-tetrahydroberberine (2a-2x) were designed, synthesized, and evaluated by lipid-lowering experiments. The results displayed that most compounds exhibited more lipid-lowering activities than berberine. Among them, compound 1m inhibited cholesterol production close to 50% in both cell models when compared with the blank control; the inhibition of triglycerides exceeded 70%. Moreover, 1m also had significant pharmacological effects on the inhibition of LDLC and promotion of HDLC production, especially in the HepG2 cell model, in which the inhibitory rate against LDLC was close to 70% and the increase rate of HDLC was more than 75%. The hypolipidemic experiment of SD rats demonstrated that after 40 days of administration (1m, 15 mg/kg/d), blood cholesterol was reduced by 19.6%, triglycerides reduced by 34.52%, and LDLC reduced by 41.49%, when compared with the high-fat diet model (HFD). In addition, after 80 days of administration, the three indexes of 1m were still better than that of berberine. Oil Red O staining and H&E staining results showed that 1m exhibited potent lipid scavenging activity. All in all, 1m was discovered and identified as a potent lipid-lowering agent and a new berberine-like candidate, being evaluated by subsequent studies.

COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING NASH, NAFLD, AND OBESITY

The present technology relates to methods of treating NASH, NAFLD and/or obesity using compounds of Formulas I, II, III, IV, V, and/or VI. The methods include administering to a subject suffering from one or more of non-alcoholic steatohepatitis (NASH), non- alcoholic fatty liver disease (NAFLD) and/or obesity a therapeutically effective amount of such a compound

Isoquinoline alkaloid as well as derivative, preparation method, pharmaceutical composition and application thereof

The invention discloses isoquinoline alkaloid as well as a derivative, a preparation method, a pharmaceutical composition and application thereof. The structure of the compound is shown as a formula I shown in the description. The isoquinoline alkaloid derivative relates to an isomer, a diastereoisomer, an enantiomer, a tautomer, a solvate, a salt of the solvate, a pharmaceutically acceptable salt or a mixture of the isomer, the diastereoisomer, the enantiomer, the tautomer, the solvate, the salt of the solvate and the pharmaceutically acceptable salt of the compound. The isoquinoline alkaloid and the derivative thereof can reduce blood fat and improve insulin resistance of a body, have obvious curative effects on a cellular level and in an animal body, and can be used for preparing a medicine for preventing and/or treating the non-alcoholic fatty liver disease, and the compound is simple and convenient in synthesis method and easy to operate.

Compounds and Compositions for Modulating Lipid Levels and Methods of Preparing Same

The present technology relates to compounds of Formulas I-VI and methods of making and using such compounds. Methods of use include prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Compounds disclosed herein also increase HDL-C, lower total cholesterol, LDL-cholesterol, and triglycerides and increase hepatic LDL receptor expression, inhibit PCSK9 expression, and activate AMP-activated protein kinase.

CORYDALINE DERIVATIVES USEFUL FOR REDUCING LIPID LEVELS

The present technology relates to compounds of Formulas (V) and (VI) and methods of making and using such compounds. Methods of use include prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Compounds disclosed herein also lower total cholesterol, LDL- cholesterol, and triglycerides and increase hepatic LDL receptor expression, inhibit PCSK9 expression, and activate AMP-activated potein kinase.

COMPOUNDS, COMPOSITIONS AND METHODS FOR REDUCING LIPID LEVELS

Compositions comprising extracts or isolated or purified compounds from plants of the genus Corydalis provide prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome. Corydalis compounds and their derivatives of natural and synthetic origins lower total cholesterol, LDL-cholesterol, and triglycerides and increase hepatic LDL receptor expression and activate AMP-activated protein kinase. Specific stereoisomers of Corydalis compounds with lipid lowering activity include 14R-(+)-corypalmine, 14R,13S-(+)-corydaline, 14R-(+)-tetrahydropalmatin, (+)-corlumidin, d-(+)-bicuculline, and (+)-egenine.