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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10402 - Inorganic and nuclear chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2018

Confidentiality

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

Name of the periodical

Dalton Transactions

ISSN

1477-9226

e-ISSN

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Volume of the periodical

47

Issue of the periodical within the volume

48

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

17367-17381

UT code for WoS article

000453550900018

EID of the result in the Scopus database

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