A new method for determination of the activity of phenanthrene-9,10-epoxidase, one of the monoxygenases of the system of drug metabolism, in rat liver microsomes was developed. The method includes the use of phenanthrene as substrate. The rate of the substrate epoxidation is measured with the help of HPLC reverse phase in accordance with the method of the internal standard (1-naphthol) by 9,10-dihydroxy-9,10-dihydrophenanthrene, a product of the intermediate epoxide hydrolysis. For rapid quantitative conversion of the formed 9,10-epoxy-9,10-dihydrophenanthrene endogenic epoxide hydrolase is used after selective termination of the monoxygenase reaction. The time of the assay by HPLC is 4.5 minutes. Phenobarbital is a more strong and selective inductor of this form of cytochrome P-450 than 3-methylcholanthrene. The simultaneous use of the two inductors does not result in additive increasing of the enzyme activity.
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Eur J Med Chem
January 2025
Jiangsu Key Laboratory of Drug Design & Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:
The bromodomain-containing protein 4 (BRD4) is an epigenetic regulatory 'reader' belonging to the bromodomain and extra-terminal domain (BET) family. Several studies have demonstrated that the high expression of BRD4 is closely related to the occurrence and development of various cancers, so BRD4 has become a promising target for cancer treatment. However, there are no drugs targeting BRD4 available on the market, the development of novel BRD4 inhibitors is of great significance.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, China; Institute of Flow Chemistry and Engineering, School of Chemistry and Materials, Jiangxi Normal University, Nanchang, 330022, China. Electronic address:
In order to enhance the anti-HIV-1 potency and selectivity of the previously reported compound 3 (EC = 27 nM, SI = 1361), a series of novel biphenyl-diarylpyrimidine derivatives were developed by employing structure-based drug design strategy. Among these derivatives, compound M44 demonstrated the most potent inhibitory activity against wild-type (WT) HIV-1 as well as five drug-resistant mutants (EC = 5-148 nM), which were 5-173 times more potent than that of 3 (EC = 27-9810 nM). Furthermore, this analogue exhibited approximately 11-fold lower cytotoxicity (CC = 54 μM) than that of etravirine and rilpivirine.
View Article and Find Full Text PDFChem Res Toxicol
January 2025
Collaborations Pharmaceuticals, Inc., 1730 Varsity Drivef, Suite 360, Raleigh, North Carolina 27606-5228, United States.
We have assessed the human liver microsomal (HLM) metabolism of the chemical warfare nerve agents' sarin (GB), cyclosarin (GF), and the Novichok agents A-230 and A-232. In HLM, GB showed drastically decreased stability ( = 1.4 h).
View Article and Find Full Text PDFChem Res Toxicol
January 2025
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, P.R. China.
Apatinib, a commonly used tyrosine kinase inhibitor in cancer treatment, can cause adverse reactions such as hypertension. Hypertension, in turn, can increase the risk of certain cancers. The coexistence of these diseases makes the use of combination drugs more common in clinical practice, but the potential interactions and regulatory mechanisms in these drug combinations are poorly understood.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
December 2024
School of Pharmaceutical Sciences, Guizhou Medical University Guiyang 550004, China Engineering Research Center for Development and Application of Ethnic Medicine and Traditional Chinese Medicine, Guizhou Medical University Guiyang 550004, China.
This study aims to compare the metabolic differences of baicalin and its analogues between Shuganning Injection and Scutellariae Radix extract. Twelve SD rats were randomly divided into a Shuganning Injection group and a Scutellariae Radix extract group, with 6 rats in each group. Their liver microsomes were incubated with the drugs, and then the samples were collected.
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