71266-78-9Relevant academic research and scientific papers
8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models
Cheng, Zhe,Chen, An-Feng,Wu, Fang,Sheng, Li,Zhang, Han-Kun,Gu, Min,Li, Yuan-Yuan,Zhang, Li-Na,Hu, Li-Hong,Li, Jing-Ya,Li, Jia
, p. 5915 - 5924 (2010)
The clinical use of the natural alkaloid berberine (BBR) as an antidiabetic reagent is limited by its poor bioavailability. Our previous work demonstrated that dihydroberberine (dhBBR) has enhanced bioavailability and in vivo efficacy compared with berberine. Here we synthesized the 8,8-dimethyldihydroberberine (Di-Me) with improved stability, and bioavailability over dhBBR. Similar to BBR and dhBBR, Di-Me inhibited mitochondria respiration, increased AMP:ATP ratio, activated AMPK and stimulated glucose uptake in L6 myotubes. In diet-induced obese (DIO) mice, Di-Me counteracted the increased adiposity, tissue triglyceride accumulation and insulin resistance, and improved glucose tolerance at a dosage of 15 mg/kg. Administered to db/db mice with a dosage of 50 mg/kg, Di-Me effectively reduced random fed and fasting blood glucose, improved glucose tolerance, alleviated insulin resistance and reduced plasma triglycerides, with better efficacy than dhBBR at the same dosage. Our work highlights the importance of dihydroberberine analogs as potential therapeutic reagents for type 2 diabetes treatment.
8,8-Dialkyldihydroberberines with potent antiprotozoal activity
Endeshaw, Molla,Zhu, Xiaohua,He, Shanshan,Pandharkar, Trupti,Cason, Emily,Mahasenan, Kiran V.,Agarwal, Hitesh,Li, Chenglong,Munde, Manoj,Wilson, W. David,Bahar, Mark,Doskotch, Raymond W.,Kinghorn, A. Douglas,Kaiser, Marcel,Brun, Reto,Drew, Mark E.,Werbovetz, Karl A.
, p. 311 - 315 (2013)
Semisynthetic 8,8-dialkyldihydroberberines (8,8-DDBs) were found to possess mid- to low-nanomolar potency against Plasmodium falciparum blood-stage parasites, Leishmania donovani intracellular amastigotes, and Trypanosoma brucei brucei bloodstream forms. For example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro IC50 values of 77, 100, and 5.3 nM against these three parasites, respectively. In turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-DDBs, were much less potent against these parasites in vitro. While the natural product berberine is a weak DNA binder, the 8,8-DDBs displayed no affinity for DNA, as assessed by changes in the melting temperature of poly(dA·dT) DNA. Selected 8,8-DDBs showed efficacy in mouse models of visceral leishmaniasis and African trypanosomiasis, with 8,8-dimethyldihydroberberine chloride (5a) reducing liver parasitemia by 46% in L. donovani-infected BALB/c mice when given at an intraperitoneal dose of 10 mg/kg/day for five days. The 8,8-DDBs may thus serve as leads for discovering new antimalarial, antileishmanial, and antitrypanosomal drug candidates.
NOVEL ISOQUINOLINE DERIVATIVES
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Page/Page column 40, (2010/11/18)
A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R7 have the significance given in claim 1, can be used in the form of a pharmaceutical composition.
NOVEL ISOQUINOLINE DERIVATIVES
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Page/Page column 22, (2010/12/29)
The invention provides novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R7 are as described herein, compositions including the compounds and methods of preparing and using the compounds.
