Synthesis of naphthalimide-carborane and metallacarborane conjugates: Anticancer activity, DNA binding ability
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388980%3A_____%2F20%3A00520191" target="_blank" >RIV/61388980:_____/20:00520191 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/20:10421736
Result on the web
<a href="http://hdl.handle.net/11104/0304879" target="_blank" >http://hdl.handle.net/11104/0304879</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bioorg.2019.103432" target="_blank" >10.1016/j.bioorg.2019.103432</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis of naphthalimide-carborane and metallacarborane conjugates: Anticancer activity, DNA binding ability
Original language description
The development of 1,8-naphthalimide derivatives as DNA-targeting anticancer agents is a rapidly growing area and has resulted in several derivatives entering into clinical trials. One of original recent developments is the use of boron clusters: carboranes and metallacarboranes in the design of pharmacologically active molecules. In this direction several naphthalimide-carborane and metallacarborane conjugates were synthesized in the present study. Their effect on a cancer cell line cytotoxicity, type of cell death, cell cycle, and ROS production were investigated. The tested conjugates revealed different activities than the leading members of the naphthalimides family, namely mitonafide and pinafide. These derivatives could induce GO/G1 arrest and promote mainly apoptosis in HepG2 cell line. Our investigations demonstrated that the most promising molecule is N-{[2-(3,3'commo-bis(1,2-dicarba-3-cobalta(III)-doso-dodecaborate-1-yeethyll-1'-aminoethyl)}-1,8-naphthalimidel (17). It was shown that 17 exhibited cytotoxicity against HepG2 cells, activated cell apoptosis, and caused cell cycle arrest in HepG2 cells. Further investigations in HepG2 cells revealed that compound 17 can also induce ROS generation, particularly mitochondrial ROS (mtROS), which was also proved by increased 8-oxo-dG level in DNA. Additionally to biological assays the interaction of the new compounds with ct-DNA was studied by CD spectra and melting temperature, thus demonstrating that these compounds were rather weak classical DNA intercalators.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - 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
Result continuities
Project
<a href="/en/project/GA18-27648S" target="_blank" >GA18-27648S: New drug delivery systems to cross biological barriers based on the unique properties of carboranes</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Bioorganic Chemistry
ISSN
0045-2068
e-ISSN
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Volume of the periodical
94
Issue of the periodical within the volume
JAN
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
103432
UT code for WoS article
000505596300085
EID of the result in the Scopus database
2-s2.0-85075831277