Synthesis of naphthalimide-carborane and metallacarborane conjugates: Anticancer activity, DNA binding ability

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11310/20:10421736

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis of naphthalimide-carborane and metallacarborane conjugates: Anticancer activity, DNA binding ability

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Synthesis of naphthalimide-carborane and metallacarborane conjugates: Anticancer activity, DNA binding ability

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/GA18-27648S" target="_blank" >GA18-27648S: Nové systémy pro dopravu léčiv přes biologické bariéry založené na unikátních vlastnostech karboranů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

—

Svazek periodika

94

Číslo periodika v rámci svazku

JAN

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

103432

Kód UT WoS článku

000505596300085

EID výsledku v databázi Scopus

2-s2.0-85075831277