Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Gold(I) complexes of 9-deazahypoxanthine as selective antitumor and anti-inflammatory agents

J. Vančo, J. Gáliková, J. Hošek, Z. Dvořák, L. Paráková, Z. Trávníček,

. 2014 ; 9 (10) : e109901.

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc15022955

The gold(I) mixed-ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1-5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1-5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 (breast carcinoma), HOS (osteosarcoma), A549 (adenocarcinoma), G361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ-carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1-5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1-5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ-carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc15022955
003      
CZ-PrNML
005      
20150709122653.0
007      
ta
008      
150709s2014 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1371/journal.pone.0109901 $2 doi
035    __
$a (PubMed)25333949
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Vančo, Ján $u Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
245    10
$a Gold(I) complexes of 9-deazahypoxanthine as selective antitumor and anti-inflammatory agents / $c J. Vančo, J. Gáliková, J. Hošek, Z. Dvořák, L. Paráková, Z. Trávníček,
520    9_
$a The gold(I) mixed-ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1-5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1-5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 (breast carcinoma), HOS (osteosarcoma), A549 (adenocarcinoma), G361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ-carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1-5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1-5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ-carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds.
650    _2
$a zvířata $7 D000818
650    _2
$a antiflogistika $x chemie $x farmakologie $x terapeutické užití $7 D000893
650    _2
$a protinádorové látky $x chemie $x farmakologie $x terapeutické užití $7 D000970
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a modely nemocí na zvířatech $7 D004195
650    _2
$a edém $x farmakoterapie $7 D004487
650    _2
$a zlato $x chemie $x farmakologie $x terapeutické užití $7 D006046
650    _2
$a hepatocyty $x účinky léků $7 D022781
650    _2
$a lidé $7 D006801
650    _2
$a hypoxanthiny $x chemie $x farmakologie $x terapeutické užití $7 D007042
650    _2
$a zánět $x farmakoterapie $7 D007249
650    _2
$a nádory $x farmakoterapie $7 D009369
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a spektroskopie infračervená s Fourierovou transformací $7 D017550
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Gáliková, Jana $u Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
700    1_
$a Hošek, Jan $u Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
700    1_
$a Dvořák, Zdeněk $u Regional Centre of Advanced Technologies and Materials & Department of Cell Biology and Genetics, Faculty of Science, Palacký University, Olomouc, Czech Republic.
700    1_
$a Paráková, Lenka $u Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic.
700    1_
$a Trávníček, Zdeněk $u Regional Centre of Advanced Technologies and Materials & Department of Inorganic Chemistry, Faculty of Science, Palacký University, Olomouc, Czech Republic.
773    0_
$w MED00180950 $t PloS one $x 1932-6203 $g Roč. 9, č. 10 (2014), s. e109901
856    41
$u https://pubmed.ncbi.nlm.nih.gov/25333949 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20150709 $b ABA008
991    __
$a 20150709122712 $b ABA008
999    __
$a ok $b bmc $g 1083294 $s 905948
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2014 $b 9 $c 10 $d e109901 $i 1932-6203 $m PLoS One $n PLoS One $x MED00180950
LZP    __
$a Pubmed-20150709

Find record

Citation metrics

Archiving options