Τίτλος:
Silver complexes with heterocyclic thioamide and tertiary arylphosphane ligands: Synthesis, crystal structures, in vitro and in silico antibacterial and cytotoxic activity, and interaction with DNA
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Herein we report on the synthesis and molecular structures of six silver(I) mixed-ligand complexes containing a heterocyclic thioamide [4-phenyl-imidazole-2-thione (phimtH) or 2,2,5,5-tetramethyl-imidazolidine-4-thione (tmimdtH)] and a tertiary arylphosphane [triphenylphosphine (PPh3), tri-o-tolylphosphane (totp)] or diphosphane [(1,2-bis(diphenylphosphano)ethane (dppe), bis(2-diphenylphosphano-phenyl)ether (DPEphos) or 4,5-bis(diphenylphosphano)-9,9-dimethylxanthene) (xantphos)]. The interaction of the compounds with calf-thymus DNA (CT DNA), as monitored directly via UV–vis spectroscopy and DNA-viscosity measurements and indirectly via its competition with ethidium bromide for DNA-intercalation sites, is suggested to take place via an intercalative mode. The new complexes show selective significant in vitro antibacterial activity against four bacterial strains. The antiproliferative effects and cytostatic efficacies of the complexes against four human cancer cell lines were evaluated. The best cytostatic and cytotoxic activity was appeared for the complexes bearing the phimtH moiety. In order to explain the described in vitro activity of the complexes, and to approach a possible mechanism of action, molecular docking studies were adopted on the crystal structure of CT DNA, DNA-gyrase, human estrogen receptor alpha and a cell-cycle specific target protein, human cyclin-dependent kinase 6. © 2020 Elsevier Inc.
Συγγραφείς:
Anastasiadou, D.
Geromichalou, E.
Tsavea, E.
Psomas, G.
Hatzidimitriou, A.G.
Kalogiannis, S.
Geromichalos, G.
Trafalis, D.
Dalezis, P.
Aslanidis, P.
Περιοδικό:
Journal of Inorganic Biochemistry
Εκδότης:
ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
Λέξεις-κλειδιά:
2,2,5,5 tetramethyl imidazolidine 4 thione; 4 phenyl imidazole 2 thione; 4,5 bis(diphenylphosphano) 9,9 dimethylxanthene; antibiotic agent; bis(2 diphenylphosphano phenyl)ether; cyclin dependent kinase 6; cytostatic agent; diphosphane 1,2 bis(diphenylphosphano)ethane; DNA; DNA topoisomerase (ATP hydrolysing); estrogen receptor alpha; ethidium bromide; silver; thioamide; tri o tolylphosphane; triphenylphosphine; unclassified drug; antiinfective agent; antineoplastic agent; calf thymus DNA; CDK6 protein, human; coordination compound; cyclin dependent kinase 6; DNA; DNA topoisomerase (ATP hydrolysing); Escherichia coli protein; estrogen receptor alpha; estrogen receptor alpha, human; intercalating agent; ligand; organophosphorus compound; protein binding; silver; thioamide, antibacterial activity; antineoplastic activity; antiproliferative activity; Article; bacterial strain; cancer cell line; cell cycle; cell division; chemical interaction; clinical evaluation; computer model; crystal structure; cytotoxicity; drug DNA binding; drug mechanism; drug synthesis; female; human; human cell; in vitro study; MCF-7 cell line; molecular docking; PC-3 [Human lung carcinoma] cell line; protein expression; SK-OV-3 cell line; ultraviolet visible spectroscopy; animal; bacterium; bovine; chemistry; drug effect; metabolism; microbial sensitivity test; synthesis, Animals; Anti-Bacterial Agents; Antineoplastic Agents; Bacteria; Cattle; Coordination Complexes; Cyclin-Dependent Kinase 6; DNA; DNA Gyrase; Escherichia coli Proteins; Estrogen Receptor alpha; Humans; Intercalating Agents; Ligands; Microbial Sensitivity Tests; Molecular Docking Simulation; Organophosphorus Compounds; Protein Binding; Silver; Thioamides
DOI:
10.1016/j.jinorgbio.2020.111167
