N,N-Dialkylbenzimidazol-2-ylidene platinum complexes effects of alkyl residues and ancillary cis-ligands on anticancer activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F18%3A00501562" target="_blank" >RIV/68081707:_____/18:00501562 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1039/c8dt03360a" target="_blank" >http://dx.doi.org/10.1039/c8dt03360a</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c8dt03360a" target="_blank" >10.1039/c8dt03360a</a>

Jazyk výsledku

angličtina

Název v původním jazyce

N,N-Dialkylbenzimidazol-2-ylidene platinum complexes effects of alkyl residues and ancillary cis-ligands on anticancer activity

Popis výsledku v původním jazyce

Eleven complexes of [(1,3-dialkylbenzimidazol-2-ylidene)LnCl3-n]Pt(n-1)+, with L-n = DMSO (8), Ph3P (9), (Ph3P)(2) (10), and alkyl = Me (a), Et (b), Bu (c), octyl (d), were synthesised and tested for cellular accumulation, cytotoxicity, interference with the tumour cell cycle, and interaction with DNA. The delocalised lipophilic cationic bisphosphane complexes 10 were on average found to be more cytotoxic in MTT assays against a panel of seven cancer cell lines than the neutral DMSO and monophosphane complexes 8 and 9. The uptake of complexes 10, at least into HCT116 colon carcinoma cells, was also significantly greater than that of analogues 8 and 9. Their cytotoxicities did not differ significantly with the N-alkyl side chain length. The complexes that were most active, with sub-micromolar IC50 (72 h) values against HCT116(wt) cells, that is 8b, 9b, 10a-c, worked by a mode of action that was dependent on the functional p53, yet were still far more active than cisplatin in both of the HCT116(wt) and HCT116(-/-) variants. In detailed binding analyses 8c, 9c and 10a-c showed a lower affinity to DNA and different binding modes when compared to cisplatin, preferably forming mono-adducts with DNA and distorting it to a lower extent. Also, unlike cisplatin, they arrested the HCT116 cells of both variants predominantly in the G1 phase.

Název v anglickém jazyce

N,N-Dialkylbenzimidazol-2-ylidene platinum complexes effects of alkyl residues and ancillary cis-ligands on anticancer activity

Popis výsledku anglicky

Eleven complexes of [(1,3-dialkylbenzimidazol-2-ylidene)LnCl3-n]Pt(n-1)+, with L-n = DMSO (8), Ph3P (9), (Ph3P)(2) (10), and alkyl = Me (a), Et (b), Bu (c), octyl (d), were synthesised and tested for cellular accumulation, cytotoxicity, interference with the tumour cell cycle, and interaction with DNA. The delocalised lipophilic cationic bisphosphane complexes 10 were on average found to be more cytotoxic in MTT assays against a panel of seven cancer cell lines than the neutral DMSO and monophosphane complexes 8 and 9. The uptake of complexes 10, at least into HCT116 colon carcinoma cells, was also significantly greater than that of analogues 8 and 9. Their cytotoxicities did not differ significantly with the N-alkyl side chain length. The complexes that were most active, with sub-micromolar IC50 (72 h) values against HCT116(wt) cells, that is 8b, 9b, 10a-c, worked by a mode of action that was dependent on the functional p53, yet were still far more active than cisplatin in both of the HCT116(wt) and HCT116(-/-) variants. In detailed binding analyses 8c, 9c and 10a-c showed a lower affinity to DNA and different binding modes when compared to cisplatin, preferably forming mono-adducts with DNA and distorting it to a lower extent. Also, unlike cisplatin, they arrested the HCT116 cells of both variants predominantly in the G1 phase.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Dalton Transactions

ISSN

1477-9226

e-ISSN

—

Svazek periodika

47

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

17367-17381

Kód UT WoS článku

000453550900018

EID výsledku v databázi Scopus

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