Inhibition of human cytochrome CYP1B1 by anthraquinone compounds,chrysophanol and physcion

The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses of ethoxyresorufin.Both chrysophanol(IC_(50)(0.47±0.01)μmol·L^(-1))and physcion(IC_(50)(0.35±0.02)μmol·L^(-1))significantly reduce the catalytic efficiency of CYP1B1.The V_(max)and K_(m)values are determined to be(51.9912±10.0547)pmol·μg^(-1)(protein)·min^(-1) and(0.9663±0.2987)nmol·L^(-1)for chrysophanol,and(45.4227±1.9978)pmol·μg^(-1)(protein)·min^(-1) and(0.4367±0.0386)nmol·L^(-1)for physcion,respectively.Kinetic analysis reveals that chrysophanol and physcion exert mixed inhibitory effects on CYP1B1.This mixed inhibition is primarily characterized by the compounds’ability to competitively bind to the active sites of CYP1B1,as well as potentially through non-competitive mechanisms,thereby reducing the enzyme’s catalytic efficiency.Molecular docking studies are conducted to elucidate the interaction between anthraquinone derivatives and CYP1B1,indicating that these compounds may inhibit CYP1B1 activity by binding to their active sites.The demonstrated capacity of chrysophanol and physcion to inhibit CYP1B1 enzymatic function unveils a potential anticancer mechanism,advancing our comprehension of how the structure of anthraquinone derivatives correlates with CYP1B1 inhibition and paving the way for developing innovative cancer treatments.

Ab Initio Molecular Dynamics Simulation of Liquid Water with Fragmentbased Quantum Mechanical Approach under Periodic Boundary Conditions

In this study,we investigated the structural and dynamical properties of liquid water by using ab initio molecular dynamics simulation under periodic boundary conditions based on the fragment-based quantum mechanical approach.This study was carried out using the second-order Møller-Plesset perturbation theory(MP2)with the aug-cc-pVDZ basis set,which has been validated to be sufficiently accurate for describing water interactions.Diverse properties of liquid water,including radial distribution functions,diffusion coefficient,dipole moment,triplet oxygen-oxygen-oxygen angles,and hydrogen-bond structures,were simulated.This ab initio description leads to these properties in good agreement with experimental observations.This computational approach is general and transferable,providing a comprehensive framework for ab initio predictions of properties of condensed-phase matters.

“一带一路”背景下我国与东盟国家仿制药注册制度对比研究

近年来,在"一带一路"的大背景下我国与东盟国家医药贸易往来不断加大,药品专利到期为仿制药提供了巨大的发展空间。为推动我国与东盟国家仿制药产业的合作发展,保障人民用药可及性,本文通过文献研究对东盟仿制药申请现状进行梳理,选取东盟中与我国医药贸易往来较大的3个国家(新加坡、泰国、马来西亚)与我国进行仿制药申请制度的对比,以期为我国与东盟国家展开仿制药产业合作提供有价值的科学信息。

Development and challenges of professional Master of pharmacy education in China

In the present work,we aimed to describe the current situation and developing trend of professional Master of pharmacy education in China.Systematic searches of websites for literatures related to the specialty of professional Master of pharmacy were conducted.E-mail or telephone inquires were made directly to 108 pharmacy institutions(schools and universities)in China offering the MPharm program.The MPharm program was established in China in 2010,which primarily focuses on cultivating professionals in fields,such as drug technology transformation,inspection and regulation of drugs,registration and distribution of drugs,and pharmaceutical services.After 9 years of development,it has almost completed the overall design of its higher education paradigm with Chinese characteristics.With the rapid development of the pharmaceutical industry in China,the professional degree of pharmacy education program at the master’s level is insufficient to meet social and market demand for qualified professionals.Therefore,doctoral-level programs are now being promoted.

Cardioprotective effects of combination of notoginseng total saponins and safflower total flavonoids against myocardial infarction in rats

In this study, the cardioprotective mechanism of the combination of notoginseng total saponins and safflower total flavonoids（CNS） was investigated due to its excellently efficacy against myocardial infarction（MI） in rats. After the left anterior descending coronary artery（LADCA） ligation, rats were orally administered with CNS for 7 consecutive days. CNS prevented MI-induced pathophysiological changes and significantly decreased plasma levels of myocardial enzymes, including creatine kinase MB isoenzyme（CK-MB）, lactate dehydrogenase（LDH） and aspartate aminotransferase（AST）. Further investigation revealed that CNS attenuated the production of inflammatory factors in plasma, including tumor necrosis factor-alpha（TNF-α）, interleukin-6（IL-6） and interleukin-1β（IL-1β）. Moreover, CNS treatment decreased the expression of caspase-3 at the mR NA level in infarct tissue. Our findings demonstrated that the anti-inflammatory and anti-apoptotic properties of CNS might confer its cardioprotection against MI in rats.

Intranasal delivery of rapid-onset antidepressants:a new trend of treating major depressive disorder

Existing antidepressants seem to have an onset time of several weeks.However,newly found depression-related receptors and pathways may enlighten us to find more rapid-onset antidepressants,in which ketamine is one of the most potential antidepressants.By intranasal administration,drugs can be directly delivered to the brain via olfactory nerve route,which is proved to be suitable for some antidepressants.Well-designed rapid-onset antidepressants are the urgent requirements of the patients with depression.Intranasal administration,as a potential strategy to deliver antidepressants to brain,can improve drug efficacy and largely shorten the onset time.In this article,we sorted out some new formulation approaches in treating depression with different mechanisms and pathways compared with traditional treating strategies,along with new findings in clinical studies,proving that the combination of rapid-onset antidepressants with intranasal delivery will lead a new trend in treating depression.

Identification of unknown impurities in triamcinolone acetonide palmitate

In the present study,we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques,and these impurities were synthesized and purified by column chromatography.Based on the results of NMR spectroscopy,IR spectroscopy,and MS,the two impurities were confirmed as 9-fluoro-11β,21-dihydroxy-16α,17-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione 21-myristate and stearate,respectively.

Discovery of novel aspartate derivatives as highly potent and selective FXIa inhibitors

As a coagulation factor in the intrinsic coagulation pathway,factor XIa(FXIa)is an effective and safe target for the development of antithrombotic drugs.Many small-molecule FXIa inhibitors have been discovered,some of which are being evaluated in clinical trials.However,none of them have been approved.In the present study,a highly selective potent FXIa inhibitor with poor solubility reported in our previous work was selected as a lead compound to be further modified to improve FXIa potency and physicochemical properties.The structure-based drug design and structure-activity relationship study led to the discovery of LY8,LY17,and LY25,which demonstrated enhanced FXIa potency and maintained excellent selectivity.In addition,LY8 exhibited significantly improved aqueous solubility,suggesting that it could be a promising compound to be further evaluated.

Preclinical efficacy of a novel cyclin-dependent kinase 9 inhibitor,QHRD107 against acute myeloid leukemia

QHRD107 is a specific inhibitor of cyclin-dependent kinase 9(CDK9).It is a highly potent antiproliferative agent against leukemia cells in vitro.Oral administration of QHRD107 to mice bearing acute myeloid leukemia tumors markedly inhibited tumor growth.In Molm-13 orthotopic model,QHRD107 resulted in remarkable prolongation of animal life span.After single oral administration of QHRD107 to Molm-13 xenograft model,QHRD107 was quickly absorbed and distributed to tumor with high concentration within 1 h.Tumor half-life time(T1/2)was three times longer compared with that of plasma.Under the high exposure of QHRD107 in tumor tissue,fast down-regulation of anti-apoptotic protein Mcl-1 mRNA was noted.Reduction of Ki-67 staining in tumor tissue further demonstrated the apoptosis of tumor cells.Therefore,the results provided evidence that QHRD107 at therapeutic dose had significant antitumor activity against AML cell lines.