Jan Belza, Zdeněk Trávníček*, Ján Vančo, Michal Čajan, Jan Hošek and Zdeněk Dvořák,
{"title":"金(I)与 7-氮杂吲哚的 N-杂环羰基配合物显示出对卵巢癌细胞的体外抗增殖作用和抗炎活性","authors":"Jan Belza, Zdeněk Trávníček*, Ján Vančo, Michal Čajan, Jan Hošek and Zdeněk Dvořák, ","doi":"10.1021/acs.organomet.4c00093","DOIUrl":null,"url":null,"abstract":"<p >The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1–4), were prepared and characterized. The complexes of the composition of [Au(iPr)(L<i>n</i>)], where <i>n</i> = 1–4 for 5-fluoro-7-azaindole (<b>1</b>), 5-bromo-7-azaindole (<b>2</b>), 3-chloro-7-azaindole (<b>3</b>), and 3-iodo-7-azaindole (<b>4</b>), were further evaluated for their in vitro anticancer and anti-inflammatory activities. The results showed that complexes (<b>1</b>–<b>4</b>) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC<sub>50</sub> ≈ 4–9 μM) and <i>cisplatin</i>-resistant cell line A2780R (with IC<sub>50</sub> ≈ 7–12 μM, except for <b>2</b> with IC<sub>50</sub> > 25 μM), providing significantly higher cytotoxicity than the anticancer drug <i>cisplatin</i>. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with selectivity index values of SI > 2.5. Complex <b>4</b> showed the ability to interact with <span>l</span>-cysteine and reduced glutathione at normal extracellular and intracellular levels, respectively. Complex <b>4</b> was further studied for its cellular effects in A2780 cells using flow cytometry. The ability of complexes (<b>1</b>–<b>4</b>) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex <b>4</b> reveals comparable effects as the inflammatory drug <i>auranofin</i>.</p>","PeriodicalId":56,"journal":{"name":"Organometallics","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.organomet.4c00093","citationCount":"0","resultStr":"{\"title\":\"Gold(I) N-Heterocyclic Carbene Complexes with 7-Azaindoles Demonstrates In Vitro Antiproliferative Effects on Ovarian Cancer Cells and Anti-inflammatory Activity\",\"authors\":\"Jan Belza, Zdeněk Trávníček*, Ján Vančo, Michal Čajan, Jan Hošek and Zdeněk Dvořák, \",\"doi\":\"10.1021/acs.organomet.4c00093\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1–4), were prepared and characterized. The complexes of the composition of [Au(iPr)(L<i>n</i>)], where <i>n</i> = 1–4 for 5-fluoro-7-azaindole (<b>1</b>), 5-bromo-7-azaindole (<b>2</b>), 3-chloro-7-azaindole (<b>3</b>), and 3-iodo-7-azaindole (<b>4</b>), were further evaluated for their in vitro anticancer and anti-inflammatory activities. The results showed that complexes (<b>1</b>–<b>4</b>) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC<sub>50</sub> ≈ 4–9 μM) and <i>cisplatin</i>-resistant cell line A2780R (with IC<sub>50</sub> ≈ 7–12 μM, except for <b>2</b> with IC<sub>50</sub> > 25 μM), providing significantly higher cytotoxicity than the anticancer drug <i>cisplatin</i>. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with selectivity index values of SI > 2.5. Complex <b>4</b> showed the ability to interact with <span>l</span>-cysteine and reduced glutathione at normal extracellular and intracellular levels, respectively. Complex <b>4</b> was further studied for its cellular effects in A2780 cells using flow cytometry. The ability of complexes (<b>1</b>–<b>4</b>) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex <b>4</b> reveals comparable effects as the inflammatory drug <i>auranofin</i>.</p>\",\"PeriodicalId\":56,\"journal\":{\"name\":\"Organometallics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/epdf/10.1021/acs.organomet.4c00093\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organometallics\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.organomet.4c00093\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organometallics","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.organomet.4c00093","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
Gold(I) N-Heterocyclic Carbene Complexes with 7-Azaindoles Demonstrates In Vitro Antiproliferative Effects on Ovarian Cancer Cells and Anti-inflammatory Activity
The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1–4), were prepared and characterized. The complexes of the composition of [Au(iPr)(Ln)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3), and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anticancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 ≈ 4–9 μM) and cisplatin-resistant cell line A2780R (with IC50 ≈ 7–12 μM, except for 2 with IC50 > 25 μM), providing significantly higher cytotoxicity than the anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with selectivity index values of SI > 2.5. Complex 4 showed the ability to interact with l-cysteine and reduced glutathione at normal extracellular and intracellular levels, respectively. Complex 4 was further studied for its cellular effects in A2780 cells using flow cytometry. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug auranofin.
期刊介绍:
Organometallics is the flagship journal of organometallic chemistry and records progress in one of the most active fields of science, bridging organic and inorganic chemistry. The journal publishes Articles, Communications, Reviews, and Tutorials (instructional overviews) that depict research on the synthesis, structure, bonding, chemical reactivity, and reaction mechanisms for a variety of applications, including catalyst design and catalytic processes; main-group, transition-metal, and lanthanide and actinide metal chemistry; synthetic aspects of polymer science and materials science; and bioorganometallic chemistry.