Search results for "DISCOVERY"

showing 10 items of 4119 documents

2,3-Dihydrobenzofuran privileged structures as new bioinspired lead compounds for the design of mPGES-1 inhibitors

2016

International audience; 2,3-Dihydrobenzofurans are proposed as privileged structures and used as chemical platform to design small compound libraries. By combining molecular docking calculations and experimental verification of biochemical interference, we selected some potential inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1. Starting from low affinity natural product 1, by our combined approach we identified the compounds 19 and 20 with biological activity in the low micromolar range. Our data suggest that the 2,3-dihydrobenzofuran derivatives might be suitable bioinspired lead compounds for development of new generation mPGES-1 inhibitors with increased affinity.

0301 basic medicine300323-Dihydrobenzofuran privileged structure; Cancer; Inflammation; Molecular docking; mPGES-1 inhibitors; Biochemistry; Clinical Biochemistry; Molecular Biology; Molecular Medicine; Organic Chemistry; Drug Discovery3003 Pharmaceutical Science; 3003Amino Acid MotifsClinical BiochemistryGene ExpressionPharmaceutical Science01 natural sciencesClinical biochemistryBiochemistry[ CHIM ] Chemical SciencesProtein Structure Secondary[ SDV.CAN ] Life Sciences [q-bio]/Cancerchemistry.chemical_compoundLow affinityDrug DiscoveryEnzyme Inhibitors23-Dihydrobenzofuran privileged structure; Molecular docking; mPGES-1 inhibitors; Cancer; InflammationProstaglandin-E SynthasesCancerAnti-Inflammatory Agents Non-SteroidalBiological activityProto-Oncogene Proteins c-metIntramolecular OxidoreductasesMolecular Docking SimulationMolecular dockingMolecular Medicinelipids (amino acids peptides and proteins)Cell SurvivalStereochemistryMolecular Sequence Data2Antineoplastic Agents[SDV.CAN]Life Sciences [q-bio]/Cancer3-Dihydrobenzofuran privileged structureInhibitory Concentration 50Structure-Activity Relationship03 medical and health sciencesCell Line TumorMicrosomesHumans[CHIM]Chemical SciencesMolecular BiologyBenzofuransInflammationNatural product010405 organic chemistryDrug Discovery3003 Pharmaceutical ScienceOrganic ChemistryEpithelial CellsmPGES-1 inhibitorsCombinatorial chemistryCombined approach0104 chemical sciences030104 developmental biologychemistryDrug DesignDrug Screening Assays Antitumor
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Indicaxanthin from Opuntia Ficus Indica (L. Mill) impairs melanoma cell proliferation, invasiveness, and tumor progression.

2018

Abstract Background: A strong, reciprocal crosstalk between inflammation and melanoma has rigorously been demonstrated in recent years, showing how crucial is a pro-inflammatory microenvironment to drive therapy resistance and metastasis. Purpose: We investigated on the effects of Indicaxanthin, a novel, anti-inflammatory and bioavailable phytochemical from Opuntia Ficus Indica fruits, against human melanoma both in vitro and in vivo. Study Design and Methods: The effects of indicaxanthin were evaluated against the proliferation of A375 human melanoma cell line and in a mice model of cutaneous melanoma. Cell proliferation was assessed by MTT assay, apoptosis by Annexin V-Fluorescein Isothio…

0301 basic medicine3003MaleSkin NeoplasmsPyridinesPyridinePhytochemicalsMelanoma ExperimentalPharmaceutical ScienceIndicaxanthinApoptosisBcl-2 B cell lymphoma gene-2 (Bcl-2)chemistry.chemical_compoundMice0302 clinical medicineOpuntia Ficus Indica (L.Mill)Settore BIO/10 - BiochimicaDrug DiscoveryCXCL1 chemokine (C-X-C motif) ligand 1MelanomaNF-κB nuclear factor kappa BMTT 3-[45-dimethyltiazol-2-yl]-25-diphenyl tetrazolium bromideMelanomaNF-kappa BOpuntiaComplementary and Alternative Medicine2708 DermatologyBetaxanthinsCXCL1030220 oncology & carcinogenesisMolecular MedicinePhC phytochemicalGrowth inhibitionIndicaxanthinHumanBiologyPhytochemicalNHEM normal human epidermal melanocyte03 medical and health sciencesc-FLIP FLICE-inhibitory proteinIn vivoCell Line TumormedicineAnimalsHumansNeoplasm InvasivenessSkin NeoplasmCell ProliferationNeoplasm InvasiveneInflammationPharmacologyCell growthAnimalDrug Discovery3003 Pharmaceutical ScienceApoptosimedicine.diseaseMice Inbred C57BL030104 developmental biologyComplementary and alternative medicinechemistryTumor progressionList of Abbrevations: AxV-FITC annexin V-fluorescein isothiocyanateBetaxanthinFruitCutaneous melanomaCancer researchPI propidium iodide PIPhytomedicine : international journal of phytotherapy and phytopharmacology
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An overview on the recent developments of 1,2,4-triazine derivatives as anticancer compounds

2017

The synthesis, the antitumor activity, the SAR and, whenever described, the possible mode of action of 1,2,4-triazine derivatives, their N-oxides, N,. N'-dioxides as well as the benzo- and hetero-fused systems are reported. Herein are treated derivatives disclosed to literature from the beginning of this century up to 2016. Among the three possible triazine isomers, 1,2,4-triazines are the most studied ones and many derivatives having remarkable antitumor activity have been reported in the literature and also patented reaching advanced phases of clinical trials.

0301 basic medicine4-benzotriazine124-triazineAntineoplastic AgentsChemistry Techniques SyntheticAntiproliferative activity01 natural sciences03 medical and health scienceschemistry.chemical_compoundNeoplasmsDrug DiscoveryOrganic chemistryAnimalsHumans124-triazineMode of action124-benzotriazineTriazineAntitumor activityPharmacology010405 organic chemistryChemistryTriazinesNitrogen heterocyclesDrug Discovery3003 Pharmaceutical Science1; 2; 4-benzotriazine; 1; 2; 4-triazine; Antiproliferative activity; Antitumor activity; Nitrogen heterocycles; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Organic ChemistryOrganic ChemistryGeneral MedicineCombinatorial chemistrySettore CHIM/08 - Chimica Farmaceutica0104 chemical sciences030104 developmental biologyNitrogen heterocycleDrug Screening Assays AntitumorAntitumor activity
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Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance.

2018

Abstract Background Epimagnolin A is an ingredient of the Chinese crude drug Shin-i, derived from the dried flower buds of Magnolia fargesii and Magnolia flos, which has been traditionally used for the treatment of allergic rhinitis and nasal congestion, empyema, and sinusitis. The pharmacokinetic activity of epimagnolin A remains to be evaluated. Purpose In this study, we examined the possible interactions of epimagnolin A with human ATP-binding cassette (ABC) transporter ABCB1, a membrane protein vital in regulating the pharmacokinetics of drugs and xenobiotics. Study design/methods The interaction of epimagnolin A with ABCB1 was evaluated in calcein, ATPase, and MTT assays by using Flp-I…

0301 basic medicineATP Binding Cassette Transporter Subfamily BATPasePharmaceutical ScienceATP-binding cassette transporterPharmacologyCrude drugLignans03 medical and health scienceschemistry.chemical_compound0302 clinical medicinePharmacokineticsCell Line TumorDrug DiscoverymedicineHumansEnzyme kineticsP-glycoproteinPharmacologyAdenosine TriphosphatasesbiologyAntineoplastic Agents PhytogenicDrug Resistance MultipleCalceinMolecular Docking Simulation030104 developmental biologyComplementary and alternative medicinechemistryVerapamilDrug Resistance NeoplasmMagnolia030220 oncology & carcinogenesisbiology.proteinMolecular MedicineVerapamilmedicine.drugPhytomedicine : international journal of phytotherapy and phytopharmacology
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γδ cell-based immunotherapy for cancer.

2019

Introduction: Cancer immunotherapy relies on the development of an efficient and long-lasting anti-tumor response, generally mediated by cytotoxic T cells. gamma delta T cells possess distinctive features that justify their use in cancer immunotherapy. Areas covered: Here we will review our current knowledge on the functions of human gamma delta T cells that may be relevant in tumor immunity and the most recent advances in our understanding of how these functions are regulated in the tumor microenvironment. We will also discuss the major achievements and limitations of gamma delta T cell-based immunotherapy of cancer. Expert opinion: Several small-scale clinical trials have been conducted i…

0301 basic medicineAdoptive cell transfergamma delta T celladoptive transfermedicine.medical_treatmentT cellClinical BiochemistryImmunotherapy Adoptive03 medical and health sciences0302 clinical medicineCancer immunotherapyNeoplasmsDrug DiscoveryAnimalsHumansMedicineCytotoxic T cellcancertumor microenvironmentIntraepithelial LymphocytesPharmacologyTumor microenvironmentbusiness.industryCancerImmunotherapymedicine.diseaseClinical trial030104 developmental biologymedicine.anatomical_structure030220 oncology & carcinogenesisCancer researchcytotoxicitybusiness
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Epithelial-mesenchymal transition: a new target in anticancer drug discovery

2016

The conversion of cells with an epithelial phenotype into cells with a mesenchymal phenotype, referred to as epithelial-mesenchymal transition, is a critical process for embryonic development that also occurs in adult life, particularly during tumour progression. Tumour cells undergoing epithelial-mesenchymal transition acquire the capacity to disarm the body's antitumour defences, resist apoptosis and anticancer drugs, disseminate throughout the organism, and act as a reservoir that replenishes and expands the tumour cell population. Epithelial-mesenchymal transition is therefore becoming a target of prime interest for anticancer therapy. Here, we discuss the screening and classification o…

0301 basic medicineAdultEpithelial-Mesenchymal TransitionCellPopulationAntineoplastic AgentsPharmacologyBiology03 medical and health sciences0302 clinical medicineSettore MED/04 - PATOLOGIA GENERALENeoplasmsDrug DiscoverymedicineHumanscancerEpithelial–mesenchymal transitioneducationAdult; Antineoplastic Agents; Epithelial-Mesenchymal Transition; Humans; Neoplasms; Drug Discovery; Pharmacology; Drug Discovery3003 Pharmaceutical SciencePharmacologyeducation.field_of_studyTransition (genetics)Drug discoveryDrug Discovery3003 Pharmaceutical ScienceGeneral MedicineAnticancer drugEMT target therapy chemoresistance030104 developmental biologymedicine.anatomical_structureDrug developmentApoptosis030220 oncology & carcinogenesisCancer research
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Expression of salivary biomarkers in patients with oral mucositis: evaluation by SELDI-TOF/MS.

2016

Objective: This study aims to evaluate changes in proteomic salivary profile of patients with oral mucositis after adjuvant cancer treatments. Materials and Methods: Samples were collected from patients after adjuvant cancer therapies, and were analyzed by means of SELDI/TOF. Patients were separated in two groups: patients affected by mucositis (MUCOSITIS) and patient without mucositis (NO MUCOSITIS). All patients were divided in function of the anticancer treatment: patients who had radiotherapy (MUCOSITIS RADIO), had not radiotherapy (MUCOSITIS NO RADIO), had chemotherapy (MUCOSITIS CHEMO), and those who had not chemotherapy (MUCOSITIS NO CHEMO). Statistical evaluation PCA (Principal Comp…

0301 basic medicineAdultMalemedicine.medical_specialtySalivaPathologymedicine.medical_treatmentGastroenterologySELDI-TOF/MS; biomarker discovery; oral mucositis; saliva; Adult; Aged; Aged 80 and over; Biomarkers; Chemotherapy Adjuvant; Female; Humans; Male; Middle Aged; Neoplasms; Radiation Injuries; Radiotherapy Adjuvant; Saliva; Stomatitis; Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization03 medical and health sciences0302 clinical medicineInternal medicineNeoplasmsbiomarker discoverymedicineMucositisHumansRadiation InjurieRadiation InjuriesSalivaGeneral DentistryStomatitisAgedAged 80 and overChemotherapyStomatitisbusiness.industryCancerSELDI-TOF/MSBiomarkerMiddle Agedmedicine.diseaseStomatitiRadiation therapy030104 developmental biologyOtorhinolaryngologyChemotherapy Adjuvant030220 oncology & carcinogenesisSpectrometry Mass Matrix-Assisted Laser Desorption-IonizationBiomarker (medicine)NeoplasmFemaleRadiotherapy AdjuvantbusinessAdjuvantoral mucositiBiomarkersHumanOral diseases
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New approach to generating insights for aging research based on literature mining and knowledge integration.

2017

The proportion of the elderly population in most countries worldwide is increasing dramatically. Therefore, social interest in the fields of health, longevity, and anti-aging has been increasing as well. However, the basic research results obtained from a reductionist approach in biology and a bioinformatic approach in genome science have limited usefulness for generating insights on future health, longevity, and anti-aging-related research on a case by case basis. We propose a new approach that uses our literature mining technique and bioinformatics, which lead to a better perspective on research trends by providing an expanded knowledge base to work from. We demonstrate that our approach …

0301 basic medicineAgingAging and Cancerlcsh:MedicineOtologyDeafnessBioinformaticsBiochemistryField (computer science)Database and Informatics MethodsOxidative DamageKnowledge integrationBasic researchDrug DiscoveryMedicine and Health SciencesData MiningPost-Translational Modificationlcsh:ScienceHearing DisordersEnergy-Producing OrganellesGlycationReductionismMultidisciplinaryCancer Risk FactorsMitochondriaKnowledgeOncologyKnowledge baseSocial interestCellular Structures and OrganellesInformation TechnologyResearch ArticleComputer and Information SciencesDrug Research and DevelopmentBioinformaticsBioenergeticsBiologyResearch and Analysis Methods03 medical and health sciencesLead (geology)Research basedHumansPharmacologybusiness.industrylcsh:RBiology and Life SciencesProteinsCell BiologyData science030104 developmental biologyOtorhinolaryngologylcsh:QReactive Oxygen SpeciesbusinessPLoS ONE
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Coffee silverskin extract protects against accelerated aging caused by oxidative agents

2016

Nowadays, coffee beans are almost exclusively used for the preparation of the beverage. The sustainability of coffee production can be achieved introducing new applications for the valorization of coffee by-products. Coffee silverskin is the by-product generated during roasting, and because of its powerful antioxidant capacity, coffee silverskin aqueous extract (CSE) may be used for other applications, such as antiaging cosmetics and dermaceutics. This study aims to contribute to the coffee sector’s sustainability through the application of CSE to preserve skin health. Preclinical data regarding the antiaging properties of CSE employing human keratinocytes and Caenorhabditis elegans are col…

0301 basic medicineAgingAntioxidantmedicine.medical_treatmentdermaceuticPharmaceutical ScienceCoffeamedicine.disease_causeAntioxidantsAnalytical Chemistrychemistry.chemical_compound0302 clinical medicineDrug Discoveryoxidative stressFood sciencenutricosmeticCellular SenescenceRoastingChemistryOxidantsChemistry (miscellaneous)030220 oncology & carcinogenesisMolecular Medicinecoffee silverskincoffee silverskin; oxidative stress; UVC radiation; chlorogenic acid; skin health; accelerated aging; nutricosmetic; dermaceuticskin healthCell SurvivalUltraviolet Rayschlorogenic acidOxidative phosphorylationArticlelcsh:QD241-441UVC radiation03 medical and health scienceslcsh:Organic chemistryChlorogenic acidCell Line Tumorparasitic diseasesmedicineaccelerated agingAnimalsHumansPhenolsPhysical and Theoretical ChemistryCaenorhabditis elegansPlant Extractsbusiness.industryOrganic ChemistryAccelerated agingBiotechnologyOxidative StressHaCaT030104 developmental biologyReactive Oxygen SpeciesbusinessBiomarkersOxidative stress
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Triggering of Toll-like Receptors in Old Individuals. Relevance for Vaccination

2019

Aging is characterized by a general decline in a range of physiological functions, with a consequent increase in the risk of developing a variety of chronic diseases and geriatric syndromes. Additionally, increasing age is accompanied by a progressive decline in both innate and acquired immune system, referred to as immunosenescence. This impaired ability to mount an efficient immune response after exposure to microorganisms or vaccines represents a major challenge in acquiring protection against pathogens in aging. Therefore, there is still a great need for vaccines that are tailored to optimally stimulate the aged immune system, thus promoting more successful aging. Various strategies ca…

0301 basic medicineAgingCellular immunityImmunosenescencemedicine.medical_treatmentDendritic cells03 medical and health sciences0302 clinical medicineImmune systemAdjuvants ImmunologicImmunityTLRDrug DiscoverymedicineHumansAgedAged 80 and overPharmacologyImmunity CellularInnate immune systembusiness.industryToll-Like ReceptorsVaccinationImmunosenescenceAcquired immune systemVaccination030104 developmental biologyImmunologyCytokinesbusinessAdjuvant030215 immunologyCurrent Pharmaceutical Design
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