title: Diverse in vitro and in vivo anti-inflammatory effects of trichlorido-gold(III) complexes with N6-benzyladenine derivatives.
abstract: A series of gold(III) complexes involving differently substituted derivatives of a plant hormone N6-benzyladenine (HL1-5) is reported. The complexes have the general formula [Au(HL1-5)Cl3]∙nH2O (n=0 for 1, 3-5; and n=1 for 2), where N6-(2-fluorobenzyl)adenine (HL1), N6-(2-chlorobenzyl)adenine (HL2), N6-(3-chlorobenzyl)adenine (HL3), N6-(4-chlorobenzyl)adenine (HL4) and N6-(4-methylbenzyl)adenine (HL5) represent the N9-coordinated ligands. The results of thorough characterization (elemental and thermal analyses, FT-IR, Raman and NMR spectroscopies, ESI+ mass spectrometry, conductivity measurements, DFT calculations) showed that the presented complexes 1-5 involve a central gold(III) atom coordinated in a square-planar geometry by the N9 atom of the purine moiety of HL1-5 and by three chlorido ligands. The complexes (1-5) were studied in vitro for cytotoxicity and anti-inflammatory activity on LPS-activated macrophages (THP-1 cell line), and in vivo for anti-inflammatory effects (1, 2, 5) using the carrageenan-induced hind paw oedema model on rats. Surprisingly, the results on the in vitro level revealed that the complexes show negligible cytotoxicity and anti-inflammatory activity, however, the activity on the in vivo level was found to be significant, fully comparable with the utilized drug Indomethacin, or even better as compared to a gold-containing metallodrug Auranofin.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, CZ-771 46 Olomouc, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Křikavová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, CZ-771 46 Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hošek
authors.affiliation: Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1/3, CZ-612 42 Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Suchý
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, CZ-771 46 Olomouc, Czech Republic.
authors.forename: Ján
authors.initials: J
authors.lastname: Vančo
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacký University in Olomouc, 17. listopadu 12, CZ-771 46 Olomouc, Czech Republic. Electronic address: zdenek.travnicek@upol.cz.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology; D001593:Benzyl Compounds; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D006046:Gold / Q000737:chemistry*; D006614:Hindlimb; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007701:Kinetin / Q000737:chemistry*; D008024:Ligands; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D011687:Purines; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001593:Benzyl Compounds; D002712:Chlorides; D056831:Coordination Complexes; D008024:Ligands; D011687:Purines; D001310:Auranofin; D006046:Gold; C480551:benzylaminopurine; D007701:Kinetin; D007213:Indomethacin
keywords: Adenine derivatives; Anti-inflammatory; Cytotoxicity; Gold(III) complexes; TNF-α