Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 603
Filter
1.
China Journal of Chinese Materia Medica ; (24): 2667-2678, 2023.
Article in Chinese | WPRIM | ID: wpr-981371

ABSTRACT

Polysaccharides have significant immunomodulatory activity and have good development value in food and medicine fields. At present, there are many studies on the chemical structure and immune activity of polysaccharides, but the relationship between them of polysaccharides has not been fully explained, which limits the further development and utilization of polysaccharide resources. The immune activity of polysaccharides is closely related to their own structure. This paper systematically summarized the relationship between the relative molecular weight, monosaccharide composition, glycosidic bond types, chemical modification, and advanced conformation of polysaccharides and the immune regulation, aiming to provide references for the profound study of polysaccharide structure-activity relationship and utilization of polysaccharides.


Subject(s)
Monosaccharides/chemistry , Structure-Activity Relationship , Molecular Weight , Antioxidants/pharmacology , Polysaccharides/chemistry
2.
China Journal of Chinese Materia Medica ; (24): 2387-2395, 2023.
Article in Chinese | WPRIM | ID: wpr-981315

ABSTRACT

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.


Subject(s)
Lycium/chemistry , Drugs, Chinese Herbal/chemistry , Structure-Activity Relationship , Antioxidants/pharmacology , Antineoplastic Agents , Polysaccharides/chemistry
3.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 401-420, 2022.
Article in English | WPRIM | ID: wpr-939907

ABSTRACT

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.


Subject(s)
Humans , Bacterial Infections , Polysaccharides/chemistry , Structure-Activity Relationship
4.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 81-101, 2022.
Article in English | WPRIM | ID: wpr-929247

ABSTRACT

The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future. To deal with these "new challenges", scientists tend to re-pick up "old antibiotics". Fusidane-type antibiotics have been known for nearly 80 years as potent antibacterial agents against gram-positive bacteria, especially Staphylococci, and represent the only triterpene-derived antibiotic class in clinical setting. These attractive characteristics have drawn renewed attention on fusidane-type antibiotics in recent decades. Isolation, characterization, biological evaluation, as well as chemical modifications of fusidane-type antibiotics are increasingly being reported. Combinatorial biosynthesis of this type of antibiotics has been successfully utilized not only for elucidating the biosynthetic pathways, but also for expanding their structural diversity. Some isolated and synthetic compounds exhibit comparable or even more potent biological activity than fusidic acid. This review provides an overview of progress on the studies of structure and biology of fusidane-type antibiotics from 1943 to April 2021. The informative structure-activity relationship is also highlighted.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria , Biology , Structure-Activity Relationship
5.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 74-80, 2022.
Article in English | WPRIM | ID: wpr-929238

ABSTRACT

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.


Subject(s)
Animals , Anti-Inflammatory Agents/pharmacology , Biological Products/pharmacology , Indole Alkaloids/pharmacology , Porifera , Structure-Activity Relationship
6.
Mem. Inst. Oswaldo Cruz ; 115: e200179, 2020. graf
Article in English | LILACS, SES-SP | ID: biblio-1135266

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection depends on viral polyprotein processing, catalysed by the main proteinase (Mpro). The solution of the SARS-CoV-2 Mpro structure allowed the investigation of potential inhibitors. This work aims to provide first evidences of the applicability of commercially approved drugs to treat coronavirus disease-19 (COVID-19). We screened 4,334 compounds to found potential inhibitors of SARS-CoV-2 replication using an in silico approach. Our results evidenced the potential use of coagulation modifiers in COVID-19 treatment due to the structural similarity of SARS-CoV-2 Mpro and human coagulation factors thrombin and Factor Xa. Further in vitro and in vivo analysis are needed to corroborate these results.


Subject(s)
Humans , Protease Inhibitors/chemistry , Viral Nonstructural Proteins/antagonists & inhibitors , Betacoronavirus , Structure-Activity Relationship , Computer Simulation , Cysteine Endopeptidases , Coronavirus Infections/drug therapy , Coronavirus 3C Proteases , SARS-CoV-2 , COVID-19/drug therapy
7.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-828747

ABSTRACT

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
8.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-828583

ABSTRACT

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
9.
China Journal of Chinese Materia Medica ; (24): 3128-3135, 2020.
Article in Chinese | WPRIM | ID: wpr-828006

ABSTRACT

Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitterness components, multi-component bitterness superposition and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitterness components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids(bamatine, jatrorrhizine, berberine, epiberberine and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on the decoction of Coptidis Rhizoma and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on the decoction of Coptidis Rhizoma and five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the butter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.


Subject(s)
Humans , Alkaloids , Coptis , Drugs, Chinese Herbal , Molecular Docking Simulation , Structure-Activity Relationship , Taste
10.
Protein & Cell ; (12): 723-739, 2020.
Article in English | WPRIM | ID: wpr-827018

ABSTRACT

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Subject(s)
Animals , Humans , Mice , Antiviral Agents , Pharmacology , Therapeutic Uses , Betacoronavirus , Physiology , Binding Sites , Cell Line , Coronavirus Infections , Drug Therapy , Virology , Crotonates , Pharmacology , Cytokine Release Syndrome , Drug Therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Influenza A virus , Leflunomide , Pharmacology , Mice, Inbred BALB C , Orthomyxoviridae Infections , Drug Therapy , Oseltamivir , Therapeutic Uses , Oxidoreductases , Metabolism , Pandemics , Pneumonia, Viral , Drug Therapy , Virology , Protein Binding , Pyrimidines , RNA Viruses , Physiology , Structure-Activity Relationship , Toluidines , Pharmacology , Ubiquinone , Metabolism , Virus Replication
11.
Chinese Journal of Biotechnology ; (12): 1806-1818, 2019.
Article in Chinese | WPRIM | ID: wpr-771751

ABSTRACT

Industrial enzymes are the "chip" of modern bio-industries, supporting tens- and hundreds-fold of downstream industries development. Elucidating the relationships between enzyme structures and functions is fundamental for industrial applications. Recently, with the advanced developments of protein crystallization and computational simulation technologies, the structure-function relationships have been extensively studied, making the rational design and de novo design become possible. This paper reviews the progress of structure-function relationships of industrial enzymes and applications, and address future developments.


Subject(s)
Biocatalysis , Biotechnology , Enzymes , Chemistry , Genetics , Metabolism , Metabolic Engineering , Protein Engineering , Structure-Activity Relationship
12.
Chinese Journal of Biotechnology ; (12): 1829-1842, 2019.
Article in Chinese | WPRIM | ID: wpr-771749

ABSTRACT

Industrial enzymes have become the core "chip" for bio-manufacturing technology. Design and development of novel and efficient enzymes is the key to the development of industrial biotechnology. The scientific basis for the innovative design of industrial catalysts is an in-depth analysis of the structure-activity relationship between enzymes and substrates, as well as their regulatory mechanisms. With the development of bioinformatics and computational technology, the catalytic mechanism of the enzyme can be solved by various calculation methods. Subsequently, the specific regions of the structure can be rationally reconstructed to improve the catalytic performance, which will further promote the industrial application of the target enzyme. Computational simulation and rational design based on the analysis of the structure-activity relationship have become the crucial technology for the preparation of high-efficiency industrial enzymes. This review provides a brief introduction and discussion on various calculation methods and design strategies as well as future trends.


Subject(s)
Biocatalysis , Biotechnology , Enzymes , Chemistry , Metabolism , Metabolic Engineering , Protein Engineering , Structure-Activity Relationship
13.
China Journal of Chinese Materia Medica ; (24): 2532-2537, 2019.
Article in Chinese | WPRIM | ID: wpr-773230

ABSTRACT

According to drug design flattening principle,a series of novel indole podophyllotoxin derivatives which were introduced different indole substituents in C-4 position on the basis of podophyllotoxin nucleus were synthesized with the starting material podophyllotoxin and 1 H-indole-5-carboxylic acid. Its anti-tumor activity in vitro was tested in order to screen for high-efficiency and low-toxic compounds. Six target compounds were synthesized,and were confirmed by~1 H-NMR,~(13)C-NMR,HR-ESI-MS and melting point determination analysis. All these target compounds were not reported by previous literature. Using etoposide as positive control drug,all the target compounds were screened for cytotoxicity against He La cells,K562 cells and K562/A02 cell in vitro by MTT method. The antitumor activity screening results showed that compounds 4 b,4 e,4 f exhibited higher inhibitory rate against He La cells and K562 cells than those of control drug VP-16. This route has the advantages on simple operation and reasonable design,provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Drug Screening Assays, Antitumor , HeLa Cells , Indoles , Pharmacology , K562 Cells , Podophyllotoxin , Pharmacology , Structure-Activity Relationship
14.
Journal of Southern Medical University ; (12): 253-256, 2019.
Article in Chinese | WPRIM | ID: wpr-772090

ABSTRACT

B cell linker (BLNK) is a key linker protein of B cell receptor (BCR) signaling pathway. BLNK participates in the regulation of PLC-γactivity and the activation of Ras pathway through its typical structure and interaction network with other proteins, and is thus widely involved in the regulation of B cell proliferation, differentiation, apoptosis and signal transduction. Furthermore, it is closely related to anaphylactic diseases, multiple sclerosis, chromosomal aneuploidy, aneuglobulinemia, B lymphocytic leukemia and lymphoma. Herein we review the structure and biological function of BLNK and its role in B cell-related diseases. BLNK can cooperate with a series of effective proteins to activate BCR signaling pathway, thereby regulating the development, maturation and function of B cells. The functional mutation of BLNK can destroy the homeostasis of B cells and affect the development and maturation of B cells, which leads to the occurrence of B cell related diseases. A comprehensive understanding of the biological functions of BLNK not only provides insights into the pathogenesis of B cell-related diseases, but also inspires new ideas and helps to find breakthroughs for the treatment of these diseases with BLNK as the therapeutic target.


Subject(s)
Humans , Adaptor Proteins, Signal Transducing , Chemistry , Genetics , Physiology , Apoptosis , B-Lymphocytes , Cell Biology , Physiology , Cell Differentiation , Cell Proliferation , Mutation , Receptors, Antigen, B-Cell , Chemistry , Physiology , Signal Transduction , Structure-Activity Relationship
15.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 15-21, 2019.
Article in English | WPRIM | ID: wpr-776910

ABSTRACT

Protein tyrosine phosphatase 1B (PTP1B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii (Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1B inhibitory ursane-type triterpenes: ursolic acid (1), 2-oxopomolic acid (2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Kinetics analyses revealed that 1 was a non-competitive PTP1B inhibitor, and 2 and 3 were mixed type PTP1B inhibitors. Compounds 1-3 and structurally related triterpenes (4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases (TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxy-urs-12-ene-28-oic acid (5), and pomolic acid-3β-acetate (6) bound at the allosteric site including α3, α6, and α7 helix of PTP1B.


Subject(s)
Humans , Enzyme Inhibitors , Chemistry , Metabolism , Fruit , Chemistry , Kinetics , Methanol , Chemistry , Molecular Docking Simulation , Molecular Structure , Plant Extracts , Chemistry , Protein Binding , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Metabolism , Protein Tyrosine Phosphatases , Rubus , Chemistry , Structure-Activity Relationship , Triterpenes , Chemistry , Metabolism
16.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 469-474, 2019.
Article in English | WPRIM | ID: wpr-776864

ABSTRACT

Withaminimas A-F (1-6), six new withaphysalin-type withanolides were isolated from the aerial parts of Physalis minima L.. The structures of these compounds were elucidated through a variety of spectroscopic techniques including HR-MS, NMR, and ECD. Compound 1 belongs to rare 18-norwithanolides, and 2-3 were 13/14-secowithanolides. According to the traditional usage of P. minima, inhibitory effects on nitric oxide (NO) production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated, and compounds 1-4 exhibited significant inhibitory effects with IC values among 3.91-18.46 μmol·L.


Subject(s)
Animals , Mice , Anti-Inflammatory Agents , Chemistry , Pharmacology , Drugs, Chinese Herbal , Chemistry , Pharmacology , Lipopolysaccharides , Pharmacology , Macrophages , Allergy and Immunology , Molecular Structure , Physalis , Chemistry , Structure-Activity Relationship , Withanolides , Chemistry , Pharmacology
17.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 774-781, 2018.
Article in English | WPRIM | ID: wpr-812351

ABSTRACT

A series of berberine derivatives were synthesized by introducing substituted benzyl groups at C-9. All these synthesized compounds (4a-4m) were screened for their in vitro antibacterial activity against four Gram-positive bacteria and four Gram-negative bacteria and evaluated for their antifungal activity against three pathogenic fungal strains. All these compounds displayed good antibacterial and antifungal activities, compared to reference drugs including Ciprofloxacin and Fluconazole; Compounds 4f, 4g, and 4l showed the highest antibacterial and antifungal activities. Moreover, all the synthesized compounds were docked into topoisomerase II-DNA complex, which is a crucial drug target for the treatment of microbial infections. Docking results showed that H-bond, π-π stacked, π-cationic, and π-anionic interactions were responsible for the strong binding of the compounds with the target protein-DNA complex.


Subject(s)
Anti-Bacterial Agents , Chemistry , Pharmacology , Antifungal Agents , Chemistry , Pharmacology , Bacteria , Berberine , Chemistry , Pharmacology , Drug Design , Fungi , Molecular Docking Simulation , Structure-Activity Relationship
18.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 782-790, 2018.
Article in English | WPRIM | ID: wpr-812350

ABSTRACT

A series of new hybrids of dehydroandrographolide (TAD), a biologically active natural product, bearing nitric oxide (NO)-releasing moieties were synthesized and designated as NO-donor dehydroandrographolide. The biological activities of target compounds were studied in human erythroleukemia K562 cells and breast cancer MCF-7 cells. Biological evaluation indicated that the most active compound I-5 produced high levels of NO and inhibited the proliferation of K562 (IC 1.55 μmol·L) and MCF-7 (IC 2.91 μmol·L) cells, which were more potent than the lead compound TAD and attenuated by an NO scavenger. In conclusion, I-5 is a novel hybrid with potent antitumor activity and may become a promising candidate for future intensive study.


Subject(s)
Humans , Antineoplastic Agents , Chemistry , Cell Proliferation , Diterpenes , Chemistry , Pharmacology , Drug Design , Drug Screening Assays, Antitumor , K562 Cells , MCF-7 Cells , Nitric Oxide , Chemistry , Pharmacology , Structure-Activity Relationship
19.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 113-124, 2018.
Article in English | WPRIM | ID: wpr-773635

ABSTRACT

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.


Subject(s)
Animals , Female , Humans , Male , Mice , Analgesics , Chemistry , Chronic Pain , Drug Therapy , Abietanes , Chemistry , Drug Evaluation, Preclinical , Enzyme Inhibitors , Chemistry , Mice, Inbred ICR , Monoacylglycerol Lipases , Metabolism , Structure-Activity Relationship
20.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 774-781, 2018.
Article in English | WPRIM | ID: wpr-773562

ABSTRACT

A series of berberine derivatives were synthesized by introducing substituted benzyl groups at C-9. All these synthesized compounds (4a-4m) were screened for their in vitro antibacterial activity against four Gram-positive bacteria and four Gram-negative bacteria and evaluated for their antifungal activity against three pathogenic fungal strains. All these compounds displayed good antibacterial and antifungal activities, compared to reference drugs including Ciprofloxacin and Fluconazole; Compounds 4f, 4g, and 4l showed the highest antibacterial and antifungal activities. Moreover, all the synthesized compounds were docked into topoisomerase II-DNA complex, which is a crucial drug target for the treatment of microbial infections. Docking results showed that H-bond, π-π stacked, π-cationic, and π-anionic interactions were responsible for the strong binding of the compounds with the target protein-DNA complex.


Subject(s)
Anti-Bacterial Agents , Chemistry , Pharmacology , Antifungal Agents , Chemistry , Pharmacology , Bacteria , Berberine , Chemistry , Pharmacology , Drug Design , Fungi , Molecular Docking Simulation , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL