Structures and biochemical evaluation of silver(I) 5,5-diethylbarbiturate complexes with bis(diphenylphosphino)alkanes as potential antimicrobial and anticancer agents

Autor:	Pinar Sahinturk, Muhittin Aygün, Seyma Aydinlik, Jenaidullah Batur, Ceyda Icsel, Veysel T. Yilmaz
Přispěvatelé:	Uludağ Üniversitesi/Fen-Edebiyet Fakültesi/Kimya Bölümü., Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü., Uludağ Üniversitesi/Veteriner Fakültesi/Farmakoloji ve Toksikoloji Anabilim Dalı., Yılmaz, Veysel T., İçsel, Ceyda, Batur, Jenaidullah, Aydınlık, Şeyma, Şahintürk, Pınar, L-7238-2018, AAI-3342-2021, AHD-1718-2022, ABI-2909-2020
Rok vydání:	2017
Předmět:	Cytotoxicity Coordination complexes Apoptosis Antimicrobial activity 01 natural sciences Silver nitrate Cell growth Chemical structure Solid-state Gram positive bacterium Dna-binding Antineoplastic agents Drug Discovery Cell structure Molecular docking simulation Polymer G2 phase cell cycle checkpoint Antiinfective agent Cell proliferation 1 2 bis(diphenylphosphino)ethane Crystal-structures Structure activity relation Complex formation 2 2'-dipyridylamine synthesis Microbial sensitivity test General Medicine Gram-positive bacteria Antineoplastic agent Drug screening Molecular docking Dose-response relationship drug Drug stability Drug mechanism Bis(diphenylphosphino)alkane derivative Human Stereochemistry Gram negative bacterium Article Tumor cell culture Drug synthesis Anti-bacterial agents MCF cell line Dose response Humans S phase cell cycle checkpoint Drug screening assays Antitumor Pharmacology Silver 5 5 diethylbarbiturate derivative Pharmacology & pharmacy 010405 organic chemistry Crystal structure Tumor cells cultured 1 1 bis(diphenylphosphino)methane 1 4 bis(diphenylphosphino)butane Hydrogen peroxide 0104 chemical sciences Bovine serum albumin Human cell chemistry Barbiturates Barbiturate derivatives DNA damage Unclassified drug Bacterial strain Drug structure Microbial sensitivity tests Silver(I) Apoptosis mechanism Thiobarbituric Acid Crystal Structure DMV Barbituric acid derivative Synthesis chemistry.chemical_compound Cytosolic fraction Cellular uptake 5 5-Diethylbarbiturate DNA cleavage biology Serum-albumin Chemistry Anticancer 1 3 bis(diphenylphosphino)propane Gram-negative bacteria Sulfadiazine silver Alkane derivative Mitochondrial membrane potential Chemistry medicinal Coordination compound Cell death Silver Coordination polymer Breast-cancer cells 010402 general chemistry Hydrophobic effect Lipophilicity Bis(diphenylphosphino)alkane DNA binding Antineoplastic activity Apoptosis assay Drug effects Biological activity Organic Chemistry X ray crystallography Structure-activity relationship Nonhuman biology.organism_classification Antibacterial Cytosol Binding affinity Growth inhibition Biochemical analysis Antimicrobial Molecular structure Reactive oxygen metabolite Controlled study DNA Bacteria
Zdroj:	European Journal of Medicinal Chemistry. 139:901-916
ISSN:	0223-5234
DOI:	10.1016/j.ejmech.2017.08.062
Popis:	New 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. (C) 2017 Elsevier Masson SAS. All rights reserved.
Databáze:	OpenAIRE
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