92340-57-3Relevant academic research and scientific papers
Evaluation of MTBH, a novel hesperetin derivative, on the activity of hepatic cytochrome P450 isoform in?vitro and in?vivo using a cocktail method by HPLC-MS/MS
Qin, Yan,Dong, Haijun,Sun, Jiayin,Zhang, Yilong,Li, Jun,Zhang, Tianci,Chen, Guanjun,Wang, Sheng,Song, Shuai,Wang, Wei,Fan, Yuru,Wang, Jie,Huang, Xiaohui,Shen, Chenlin
, p. 1389 - 1399 (2022/01/11)
1. 8-methylene-tert-butylamine-3′,5,7-trihydroxy-4′-methoxyflavanone (MTBH), a novel hesperidin derivative, has potential in the prevention of hepatic disease, however, its effects on cytochrome P450 isoforms (CYP450s) remains unexplored. The purpose was to investigate the effects of MTBH on the mRNA, protein levels, and activities of six CYP450s (1A2, 2C11/9, 2D2/6, 3A1/4, 2C13/19, and 2E1) in?vitro and in?vivo. 2. In vitro study, rat and human liver microsomes were adopted to elucidate the inhibitory effect of MTBH on six CYP450s using probe drugs. In vivo study, Sprague-Dawley male rats were treated with MTBH (25, 50, or 100 mg/kg for 28 consecutive days), phenobarbital (80 mg/kg for 12 consecutive days), or 0.5% CMC-Na solution (control group) by intragastric administration, then, the mRNA, protein levels and activities of liver CYP450s were analysed by real-time PCR, western blotting and probe-drug incubation systems, respectively. 3. The in?vitro study indicated that MTBH inhibits the activities of CYP3A1/4 and CYP2E1 in rat and human liver microsomes. In vivo data showed that MTBH inhibits mRNA, protein levels, and activities of CYP3A1 and CYP2E1 in medium- and high-dose MTBH groups. 4. MTBH has the potential to cause drug-drug interactions when co-administered with drugs that are metabolised by CYP3A1/4 and CYP2E1.
Acetylshikonin is a novel non-selective cytochrome P450 inhibitor
Shon, Jong Cheol,Phuc, Nguyen Minh,Kim, Won Cheol,Heo, Jae Kyung,Wu, Zhexue,Lee, Hyunyoung,Liu, Kwang-Hyeon
, p. 553 - 556 (2017/12/15)
Acetylshikonin is a biologically active compound with anti-cancer and anti-inflammatory activity, which is isolated from the roots of Lithospermum erythrorhizoma. An inhibitory effect of acetylshikonin against CYP2J2 activity was discovered recently. Based on this result, this study was expanded to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed a strong inhibitory effect against all P450s tested with IC50 values of 1.4–4.0 μ m. Pre-incubation of acetylshikonin with HLMs and NADPH did not alter the inhibition potency, indicating that acetylshikonin is not a mechanism-based inhibitor. SKF-525A, a widely used non-specific P450 inhibitor, had no inhibitory activity against CYP1A2, 2A6, 2E1 and 2J2, while it showed an inhibitory effect against CYP2B6, CYP2C19 and 2D6 with IC50 values of 2.5, 3.6 and 0.5 μ m, respectively. Our findings indicate that acetylshikonin may be a novel general P450 inhibitor, which could replace SKF-525A.
Prepare alkylene sulfonyl-1-H-benzimidazole derivatives
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Paragraph 0032; 0033; 0070; 0071, (2016/11/24)
The invention relates to a method for preparing a sulfinyl-1-hydrogen-benzimidazole derivative. According to the invention, a 2-(1H-benzimidazole-2-methylmercapto)-4-hydroxy-pyridine derivative expressed in a general formula I is dissolved in a solvent, and under the effect of a catalyst and an additive, a hydrogen peroxide aqueous solution is used as an oxidizing agent for oxidizing reaction, so that the sulfinyl-1-hydrogen-benzimidazole derivative expressed in the general formula II (refer to the Specification) is prepared. The method has the advantages that the operation is simple, a catalyst with the harmful effect on a human body is not used, no pollution to the environment is caused, and the obtained product is higher in yield and purity, so that the method is suitable for industrialization scale production, and has important practical application value.
