Aygün, Muhittin2022-11-012022-11-012017-08-28Yılmaz, V. T. vd. (2017). ''Structures and biochemical evaluation of silver(I) 5,5-diethylbarbiturate complexes with bis(diphenylphosphino)alkanes as potential antimicrobial and anticancer agents''. European Journal of Medicinal Chemistry, 139, 901-916.0223-5234https://doi.org/10.1016/j.ejmech.2017.08.062https://www.sciencedirect.com/science/article/pii/S02235234173067481768-3254http://hdl.handle.net/11452/29283New silver(I) 5,5-diethylbarbiturate (barb) complexes with a series of bis(diphenylphosphino)alkanes such as 1,1-bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis-(diphenylphosphino)propane (dppp) and 1,4-bis(diphenylphosphino)butane (dppb) were synthesized and characterized. [Ag-2(barb)(2)(mu-dppm)(2) (1), [Ag-2(barb)(2)(mu-dppe)(DMSO)(2)] (2) and [Ag-2(barb)(2)( dppp)2](3) were binuclear, while [Ag(barb)(mu-dppb)] (4) was a coordination polymer. 1-4 effectively bind to the G/C rich region of the major groove of DNA and interact with BSA via hydrophobic interactions in accordance with molecular docking studies. All complexes displayed significant DNA cleavage in the presence of H2O2. 1-4 exhibited more specificity against Gram-positive bacteria than Gram-negative bacteria, but 2 targets both bacterial strains, being comparable to AgNO3 and silver sulfadiazine. Complex 1 has a strong growth inhibitory effect on A549 cells, while 2 and 3 exhibit considerable cytotoxicity against MCF-7 cells. The complexes showed high accumulation in the cytosol fraction of the cells. Mechanistic studies showed that 1 and 2 display effective cell growth inhibition by triggering S and G2/M phase arrest, induce apoptosis via mitochondrial pathways and also damage to DNA due to the overproduction of ROS.eninfo:eu-repo/semantics/closedAccessPharmacology & pharmacy5,5-DiethylbarbiturateAnticancerAntimicrobialApoptosis mechanismBis(diphenylphosphino)alkaneSilver(I)Breast-cancer cellsCrystal-structures2,2'-dipyridylamine synthesisBarbiturate derivativesMolecular dockingCellular uptakeSerum-albuminSolid-stateAntibacterialDna-bindingAnti-bacterial agentsAntineoplastic agentsBarbituratesCell proliferationCoordination complexesDose-response relationship, drugDrug screening assays, AntitumorGram-negative bacteriaGram-positive bacteriaHumansMicrobial sensitivity testsMolecular docking simulationMolecular structureSilverStructure-activity relationshipTumor cells, culturedArticle0004127882000692-s2.0-8502869712390191613928881285Chemistry, medicinalThiobarbituric Acid; Crystal Structure; DMV1,1 bis(diphenylphosphino)methane1,2 bis(diphenylphosphino)ethane1,3 bis(diphenylphosphino)propane1,4 bis(diphenylphosphino)butaneAlkane derivativeAntiinfective agentAntineoplastic agentBarbituric acid derivativeBis(diphenylphosphino)alkane derivativeBovine serum albuminHydrogen peroxidePolymerReactive oxygen metaboliteSilver 5,5 diethylbarbiturate derivativeSilver nitrateSulfadiazine silverUnclassified drugAntiinfective agentAntineoplastic agentBarbituric acid derivativeCoordination compoundSilverAntimicrobial activityAntineoplastic activityApoptosisApoptosis assayArticleBacterial strainBinding affinityBiochemical analysisBiological activityCell deathCell growthCell structureComplex formationControlled studyCrystal structureCytosolic fractionCytotoxicityDNA bindingDNA cleavageDNA damageDrug mechanismDrug stabilityDrug structureDrug synthesisG2 phase cell cycle checkpointGram negative bacteriumGram positive bacteriumGrowth inhibitionHumanHuman cellLipophilicityMCF cell lineMitochondrial membrane potentialMolecular dockingS phase cell cycle checkpointX ray crystallographyCell proliferationChemical structureChemistryDose responseDrug effectsDrug screeningMicrobial sensitivity testStructure activity relationSynthesisTumor cell cultureNonhuman