Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis, Characterization and ctDNA/HSA Spectroscopic Binding Properties

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F22%3A73618813" target="_blank" >RIV/61989592:15640/22:73618813 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/1420-3049/27/9/2883" target="_blank" >https://www.mdpi.com/1420-3049/27/9/2883</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules27092883" target="_blank" >10.3390/molecules27092883</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis, Characterization and ctDNA/HSA Spectroscopic Binding Properties

Popis výsledku v původním jazyce

A series of novel acridine N‐acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA—ctDNA and human serum albumin—HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD‐18Co have been evaluated. The acridine‐DNA complex 3b (‐F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA‐derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐ diphenyltetrazolium bromide or MTT assay decreased as follows 3b (‐F) &gt; 3a(‐H) &gt; 3c(‐Cl) &gt; 3d(‐Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine‐benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.

Název v anglickém jazyce

Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis, Characterization and ctDNA/HSA Spectroscopic Binding Properties

Popis výsledku anglicky

A series of novel acridine N‐acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA—ctDNA and human serum albumin—HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD‐18Co have been evaluated. The acridine‐DNA complex 3b (‐F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA‐derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐ diphenyltetrazolium bromide or MTT assay decreased as follows 3b (‐F) &gt; 3a(‐H) &gt; 3c(‐Cl) &gt; 3d(‐Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine‐benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

MOLECULES

ISSN

1420-3049

e-ISSN

—

Svazek periodika

27

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

31

Strana od-do

"nečíslováno"

Kód UT WoS článku

000796147400001

EID výsledku v databázi Scopus

2-s2.0-85129860812