47,823 results match your criteria potent inhibitory

Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents.

Eur J Med Chem 2021 Apr 28;221:113480. Epub 2021 Apr 28.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, 250012, China. Electronic address:

With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. Read More

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Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents.

Bioorg Chem 2021 Apr 27;112:104947. Epub 2021 Apr 27.

Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Riyadh, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. Electronic address:

Vascular endothelial growth factor-2 (VEGFR-2) is considered one of the most important factors in tumor angiogenesis, and consequently a number of anticancer therapeutics have been developed to inhibit VEGFR-2 signaling. Accordingly, eighteen derivatives of thieno[2,3-d]pyrimidines having structural characteristics similar to VEGFR-2 inhibitors were designed and synthesized. Anticancer activities of the new derivatives were assessed against three human cancer cell lines (HCT-116, HepG2, and MCF-7) using MTT. Read More

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Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Biochem Pharmacol 2021 May 5:114593. Epub 2021 May 5.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences, Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Read More

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Analysis of natural compounds against the activity of SARS-CoV-2 NSP15 protein towards an effective treatment against COVID-19: a theoretical and computational biology approach.

J Mol Model 2021 May 8;27(6):160. Epub 2021 May 8.

College of Computer Science and Engineering, University of Ha'il, P.O. Box 2440, Ha'il, 81411, Kingdom of Saudi Arabia.

Coronavirus infectious disease 2019 (COVID-19), a viral infection caused by a novel coronavirus (nCoV), continues to emerge as a serious threat to public health. This pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has infected globally with 1,550,000 plus deaths to date, representing a high risk to public health. No effective drug or vaccine is available to curb down this deadly virus. Read More

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A novel use for an old drug: resistance reversal in by combining dihydroartemisinin with fluconazole.

Future Microbiol 2021 May 7. Epub 2021 May 7.

Department of Pharmacy, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China.

To investigate the effects of dihydroartemisinin combined with fluconazole against and to explore the underlying mechanisms. Checkerboard microdilution assay and time-kill curve method were employed to evaluate the static and dynamic antifungal effects against . Reactive oxygen species (ROS) was measured by a fluorescent probe. Read More

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Computational study on subfamilies of piperidine derivatives: QSAR modelling, model external verification, the inter-subset similarity determination, and structure-based drug designing.

SAR QSAR Environ Res 2021 May 7:1-30. Epub 2021 May 7.

Chemometrics Laboratory, Chemistry Department, Faculty of Science, University of Kurdistan, Sanandaj, Iran.

A new subset of furan-pyrazole piperidine derivatives was used for QSAR model development. These compounds exhibit good Akt1 inhibitory activity; moreover, antiproliferative activities in vitro against OVCAR-8 (Human ovarian carcinoma cells) and HCT116 (human colon cancer cells), were confirmed for them. Based on the relevant three-dimensional (3D) and 2D autocorrelation descriptors, selected by genetic algorithm (GA), multiple linear regression (MLR) was established on half maximal-inhibitory concentration (IC), in Akt1 and cancer cell lines independently. Read More

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A new oleanane-skeleton triterpene isolated from .

Nat Prod Res 2021 May 7:1-7. Epub 2021 May 7.

Department of Chemical Technology, Ho Chi Minh University of Technology and Education, Ho Chi Minh City, Vietnam.

Extensive fractionation of -hexane extract from the dried powdered-trunks of Pierre ex A.Froehner (Rubiaceae) led to the isolation of a new oleanane-skeleton triterpene, coffecanolic acid (), along with three known analogues sumaresinolic acid (), oleanolic acid (), and 3--acetyloleanolic acid (). The chemical structures were elucidated using FT-IR, 1D and 2D NMR and HR-ESI-MS data analysis. Read More

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OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo.

Drug Des Devel Ther 2021 30;15:1797-1810. Epub 2021 Apr 30.

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Purpose: OSU-03012 is a celecoxib derivative lacking cyclooxygenase-2 inhibitory activity and a potent PDK1 inhibitor which has been shown to inhibit tumor growth in various ways. However, the role of OSU-03012 in endometrial carcinoma (EC) in which the PI3K/Akt signaling pathway highly activated has not been studied. Here, we determined the potency of OSU-03012 in suppressing EC progression in vitro and in vivo, and studied the underlined mechanisms. Read More

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Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides.

Comput Biol Chem 2021 Apr 23;92:107487. Epub 2021 Apr 23.

Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Malaysia. Electronic address:

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting about 0.24 % of the world population. Protein arginine deiminase type 4 (PAD4) is believed to be responsible for the occurrence of RA by catalyzing citrullination of proteins. Read More

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Identification of non-covalent 3C-like protease inhibitors against severe acute respiratory syndrome coronavirus-2 via virtual screening of a Korean compound library.

Bioorg Med Chem Lett 2021 May 3:128067. Epub 2021 May 3.

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34113, Republic of Korea. Electronic address:

The outbreak of coronavirus (CoV) disease 2019 (COVID-19) caused by the severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has turned into a pandemic. The enzyme 3C-like protease (3CL) is essential for the maturation of viral polyproteins in SARS-CoV-2 and is therefore regarded as a key drug target for treating the disease. To identify 3CL inhibitors that can suppress SARS-CoV-2 replication, we performed a virtual screening of 500,282 compounds in a Korean compound bank. Read More

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Facile Synthesis of Imidazolium-Based Block Copolypeptides with Excellent Antimicrobial Activity.

Biomacromolecules 2021 May 6. Epub 2021 May 6.

Key Laboratory of Polymeric Materials and Application Technology of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan, Hunan 411105, China.

Antimicrobial polypeptides are promising mimics of antimicrobial peptides (AMPs) with low risks of antimicrobial resistance (AMR). Polypeptides with facile and efficient production, high antimicrobial activity, and low toxicity toward mammalian cells are highly desirable for practical applications. Herein, triblock copolypeptides with chloro groups (PPG-PCPBLG) and different main-chain lengths were synthesized via an ultrafast ring-opening polymerization (ROP) using a macroinitiator, namely poly(propylene glycol) bis(2-aminopropyl ether), and purified or nonpurified monomer (i. Read More

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Inspiratory Muscle Responses to Sudden Airway Occlusion in Chronic Obstructive Pulmonary Disease.

J Appl Physiol (1985) 2021 May 6. Epub 2021 May 6.

Neuroscience Research Australia, Australiagrid.250407.4.

Brief airway occlusion produces a potent reflex inhibition of inspiratory muscles that is thought to protect against aspiration. Its duration is prolonged in asthma and obstructive sleep apnea. We assessed this inhibitory reflex (IR) in chronic obstructive pulmonary disease (COPD). Read More

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Synthesis of Chimeric Thiazolo-Nootkatone Derivatives as Potent Antimicrobial Agents.

ChemMedChem 2021 May 6. Epub 2021 May 6.

Arkansas State University, Chemistry and Physics, PO Box 419, 72404, Jonesboro, UNITED STATES.

Nootkatone, an approved insecticide, is a well-known natural product from grapefruit. A series of fused-thiazole derivatives of nootkatone have been synthesized and these new compounds were tested against several strains of bacteria. Some of these compounds (15 and 16) are found to be potent antimicrobial agents against Staphylococcus aureus and Enterococcus faecium with minimum inhibitory concentration (MIC) values as low as 1. Read More

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Synthesis and biological evaluation of novel isoxazole-piperazine hybrids as potential anti-cancer agents with inhibitory effect on liver cancer stem cells.

Eur J Med Chem 2021 Apr 24;221:113489. Epub 2021 Apr 24.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey. Electronic address:

In our effort for the development of novel anticancer therapeutics, a series of isoxazole-piperazine analogues were prepared, and primarily screened for their antiproliferative potential against hepatocellular carcinoma (HCC; Huh7/Mahlavu) and breast (MCF-7) cancer cells. All compounds demonstrated potent to moderate cytotoxicity on all cell lines with IC values in the range of 0.09-11. Read More

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Molecular docking of compounds from extract detected by GC-MS analysis with the SARS-CoV-2 main protease and ACE2 protein.

Nat Prod Res 2021 May 5:1-5. Epub 2021 May 5.

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Penang, Malaysia.

has been reported to have many medicinal properties and it is traditionally used in treating viral lesions. This study aims to determine the molecular docking of compounds detected by Gas Chromatography-Mass Spectrometry (GC-MS) with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 main protease) protein and its host receptor angiotensin-converting enzyme 2 (ACE2) protein using the AutoDock 4.2 tool. Read More

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TSL-1502, a glucuronide prodrug of a poly (ADP-ribose) polymerase (PARP) inhibitor, exhibits potent anti-tumor activity in preclinical models.

Am J Cancer Res 2021 15;11(4):1632-1645. Epub 2021 Apr 15.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences 555 Zuchongzhi Road, Shanghai 201203, China.

Poly (ADP-ribose) polymerase (PARP) enzymes play an important role in the cellular response to DNA damage and the inhibition of PARP causes synthetic lethality in homologous recombination (HR)-deficient cancer. Multiple PARP inhibitors have been developed and have shown remarkable clinical benefits. However, treatment-related toxicities, especially the hematologic toxicities, are common and restrict the clinical applications of PARP inhibitors. Read More

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Enhancing a Natural Killer: Modification of NK Cells for Cancer Immunotherapy.

Cells 2021 Apr 29;10(5). Epub 2021 Apr 29.

Cartherics Pty Ltd., Clayton 3168, Australia.

Natural killer (NK) cells are potent innate immune system effector lymphocytes armed with multiple mechanisms for killing cancer cells. Given the dynamic roles of NK cells in tumor surveillance, they are fast becoming a next-generation tool for adoptive immunotherapy. Many strategies are being employed to increase their number and improve their ability to overcome cancer resistance and the immunosuppressive tumor microenvironment. Read More

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Limonin Enhances the Antifungal Activity of Eugenol Nanoemulsion against In Vitro and In Vivo Tests.

Microorganisms 2021 Apr 30;9(5). Epub 2021 Apr 30.

College of Horticulture and Landscape Architecture, Southwest University, Chongqing 400716, China.

, the cause of citrus blue mold, is a pathogenic fungus that seriously affects the postharvest quality of citrus fruit and causes serious economic loss. In this study, a eugenol nanoemulsion containing limonin, an antimicrobial component from citrus seeds, was prepared using a high-pressure microfluidizer and the antifungal activity of the nanoemulsions against was evaluated based on the conidial germination rate, mycelial growth, and scanning electron microscopy analysis. The results showed that the minimum inhibitory concentration and the inhibition rate of limonin-loaded eugenol nanoemulsion was 160 μg/mL and 59. Read More

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Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors.

Eur J Med Chem 2021 Apr 24;220:113501. Epub 2021 Apr 24.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.

Lysine-specific demethylase 1 (LSD1) is a FAD-dependent enzyme, which has been proposed as a promising target for therapeutic cancer. Herein, a series of benzofuran derivatives were designed, synthesized and biochemical evaluated as novel LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds potently suppressed the enzymatic activities of LSD1 and potently inhibited tumor cells proliferation. Read More

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Novel antiadipogenic effect of menadione in 3T3-L1 cells.

Chem Biol Interact 2021 May 1:109491. Epub 2021 May 1.

Instituto de Investigaciones Bioquímicas de Bahía Blanca, Universidad Nacional Del Sur (UNS)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Argentina. Departamento de Biología, Bioquímica y Farmacia, UNS, Bahía Blanca, Argentina. Electronic address:

Inhibition of adipocyte differentiation can be used as a strategy for preventing adipose tissue expansion and, consequently, for obesity management. Since reactive oxygen species (ROS) have emerged as key modulators of adipogenesis, the effect of menadione (a synthetic form of vitamin K known to induce the increase of intracellular ROS) on 3T3-L1 preadipocyte differentiation was studied. Menadione (15 μM) increased ROS and lipid peroxidation, generating mild oxidative stress without affecting cell viability. Read More

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Synthesis of 16β-derivatives of 3-(2-bromoethyl)-estra-1,3,5(10)-trien-17β-ol as inhibitors of 17β-HSD1 and/or steroid sulfatase for the treatment of estrogen-dependent diseases.

Steroids 2021 May 1:108856. Epub 2021 May 1.

Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec - Research Center (CHUL, T4), Québec, QC, G1V4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC, G1V0A6, Canada. Electronic address:

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) and steroid sulfatase (STS) are involved in the synthesis of the most potent estrogen in the human body, estradiol (E2). These enzymes are known to play a pivotal role in the progression of estrogen-dependent diseases, such as breast cancer and endometriosis. Therefore, the inhibition of 17β-HSD1 and/or STS represents a promising avenue to modulate the growth of estrogen-dependent tumors or lesions. Read More

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Efficient Dimerization Disruption of Trypanothione Reductase by Triazole-phenyl-thiazoles.

J Med Chem 2021 May 4. Epub 2021 May 4.

Instituto de Química Médica (IQM-CSIC), c/ Juan de la Cierva 3, E-28006 Madrid, Spain.

Inhibition of trypanothione disulfide reductase (TryR) by disruption of its homodimeric interface has proved to be an alternative and unexploited strategy in the search for novel antileishmanial agents. Proof of concept was first obtained by peptides and peptidomimetics. Building on previously reported dimerization disruptors containing an imidazole-phenyl-thiazole scaffold, we now report a new 1,2,3-triazole-based chemotype that yields noncompetitive, slow-binding inhibitors of TryR. Read More

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From the Design to the Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis.

J Med Chem 2021 May 4. Epub 2021 May 4.

Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l'Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII, 27-31, Barcelona 08028, Spain.

The pharmacological inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Numerous potent sEH inhibitors (sEHIs) present adamantyl or phenyl moieties, such as the clinical candidates AR9281 or EC5026. Herein, in a new series of sEHIs, these hydrophobic moieties have been merged in a benzohomoadamantane scaffold. Read More

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A Phase 1 Study to Investigate the Effects of Cortexolone 17α-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity.

Clin Pharmacol Drug Dev 2021 May 3. Epub 2021 May 3.

St George's, University of London, London, United Kingdom.

Cortexolone 17α-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17α-propionate was found to have a weak inhibitory effect on human Ether-à-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17α-propionate is absorbed. Read More

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Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn.

J Ethnopharmacol 2021 Apr 30;276:114171. Epub 2021 Apr 30.

Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, And Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco. Electronic address:

Ethnopharmacological Relevance: Centaurium erythraea is an important medicinal plant in many countries, e.g. Morocco, Algeria, Italy, Spain, Portugal, and countries of Balkan Peninsula. Read More

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Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria.

Biol Chem 2021 Mar 11;402(4):513-524. Epub 2021 Jan 11.

School of Chemistry, University of Melbourne, Melbourne, Victoria3010, Australia.

Increasing antibiotic resistance in Gram-negative bacteria has mandated the development of both novel antibiotics and alternative therapeutic strategies. Evidence of interplay between several gastrointestinal peptides and the gut microbiota led us to investigate potential and broad-spectrum roles for the incretin hormone, human glucose-dependent insulinotropic polypeptide (GIP) against the bacteria, and . GIP had a potent disruptive action on drug efflux pumps of the multidrug resistant bacteria and strains. Read More

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Biosynthesis of Silver Nanoparticles by : Characterization, Optimization, and Biological Activities.

Front Bioeng Biotechnol 2021 15;9:633468. Epub 2021 Apr 15.

Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria, Egypt.

In this study, mycelial filtrate of BA6 was used to reduce AgNO to form silver nanoparticles (AgNPs). The effect of seven independent variables on the diameter of AgNPs was studied by applying design of experiments (DOE). At optimal conditions, the diameter of AgNPs was reduced by approximately 26. Read More

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Investigation of an ALDH1A1-specific inhibitor for suppression of weight gain in a diet-induced mouse model of obesity.

Int J Obes (Lond) 2021 May 1. Epub 2021 May 1.

Department of Comparative Medicine, University of Washington, Seattle, WA, USA.

Background: Retinoic acid (RA) controls diverse physiological functions including weight regulation and energy metabolism. It has been reported that mice lacking ALDH1A1, one of the aldehyde dehydrogenases (ALDH) that synthesize RA, are healthy and resistant to weight gain, raising the possibility that inhibiting this enzyme might treat obesity. We previously demonstrated that treatment with a pan-ALDH1A enzyme inhibitor, WIN18446, suppressed weight gain in mice fed a high-fat diet (HFD), but caused increased hepatic lipidosis and reversible male infertility. Read More

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RO4929097 regulates RANKL-induced osteoclast formation and LPS-mediated bone resorption.

Aging (Albany NY) 2021 May 2;13. Epub 2021 May 2.

Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To investigate the suppressive function of RO4929097, a potent -secretase inhibitor, on RANKL-induced osteoclastogenesis. The cytotoxicity of RO4929097 was evaluated. The suppressive effect and possible molecular mechanism of RO4929097 on RANKL-induced osteoclastogenesis was evaluated both and . Read More

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The mode of antibacterial action of quaternary N-benzylimidazole salts against emerging opportunistic pathogens.

Bioorg Chem 2021 Apr 23;112:104938. Epub 2021 Apr 23.

Department of Chemistry, Faculty of Science, University of Split, Ruđera Boškovića 33, Split, Croatia. Electronic address:

Quaternary ammonium compounds (QACs) are antimicrobial agents displaying a broad spectrum of activity due to their mechanism of action targeting the bacterial membrane. The emergence of bacterial resistance to QACs, especially in times of pandemics, requires the continuous search for new and potent QACs structures. Here we report the synthesis and biological evaluation of QACs based on imidazole derivative, N-benzylimidazole. Read More

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