Anticancer Efficacy of Antibacterial Quinobenzothiazines

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F23%3A73622850" target="_blank" >RIV/61989592:15310/23:73622850 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/2076-3417/13/5/2886" target="_blank" >https://www.mdpi.com/2076-3417/13/5/2886</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/app13052886" target="_blank" >10.3390/app13052886</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Anticancer Efficacy of Antibacterial Quinobenzothiazines

Popis výsledku v původním jazyce

The antitumor potency of a series of designed and prepared antibacterial quinobenzothiazines was evaluated against different types of human cancer cell lines, such as glioblastoma SNB-19, lung adenocarcinoma A549 and breast cancer T47D, and the activities of the compounds were compared to cisplatin and doxorubicin. 9-Propoxy-5-methyl-12H-quino[3,4-b][1,4]benzo- thiazinium chloride (4a), 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (4d) and 11-benzyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (4l) were the most active compounds; their IC50 values against all three cell lines ranged from 5.3 to 9.3 µM. The effective derivatives showed no cytotoxic effect up to 100 µM on normal human dermal fibroblasts (NHDFs). To explore the structure–activity relationship, the effect of the type/nature and position of the substituents on the tetracyclic quinobenzothiazine system on the anticancer activity was investigated. Additionally, the receptor-dependent approach was used to specify the mutual ligand–enzyme (bio)compositions that might be potentially valid for the antitumor characteristics of new quinobenzothiazine derivatives. In particular, the molecular docking procedure was applied for the most potent agents against the human breast cancer line T47D in order to obtain comprehensive knowledge about the aromatase–inhibitor binding mode. The docking study revealed that some regularities in the spatial atomic distribution and nonbonding interactions (e.g., hydrophobic patterns) can be observed for the most active molecules. The surface of the electron-rich aromatic rings of 4d and 4l molecules could also contribute to π–π stacking interactions with protoporphyrin IX (HEM) as well as to the formation of π–cation interactions with the adjacent iron cofactor.

Název v anglickém jazyce

Anticancer Efficacy of Antibacterial Quinobenzothiazines

Popis výsledku anglicky

The antitumor potency of a series of designed and prepared antibacterial quinobenzothiazines was evaluated against different types of human cancer cell lines, such as glioblastoma SNB-19, lung adenocarcinoma A549 and breast cancer T47D, and the activities of the compounds were compared to cisplatin and doxorubicin. 9-Propoxy-5-methyl-12H-quino[3,4-b][1,4]benzo- thiazinium chloride (4a), 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (4d) and 11-benzyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (4l) were the most active compounds; their IC50 values against all three cell lines ranged from 5.3 to 9.3 µM. The effective derivatives showed no cytotoxic effect up to 100 µM on normal human dermal fibroblasts (NHDFs). To explore the structure–activity relationship, the effect of the type/nature and position of the substituents on the tetracyclic quinobenzothiazine system on the anticancer activity was investigated. Additionally, the receptor-dependent approach was used to specify the mutual ligand–enzyme (bio)compositions that might be potentially valid for the antitumor characteristics of new quinobenzothiazine derivatives. In particular, the molecular docking procedure was applied for the most potent agents against the human breast cancer line T47D in order to obtain comprehensive knowledge about the aromatase–inhibitor binding mode. The docking study revealed that some regularities in the spatial atomic distribution and nonbonding interactions (e.g., hydrophobic patterns) can be observed for the most active molecules. The surface of the electron-rich aromatic rings of 4d and 4l molecules could also contribute to π–π stacking interactions with protoporphyrin IX (HEM) as well as to the formation of π–cation interactions with the adjacent iron cofactor.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Applied Sciences-Basel

ISSN

2076-3417

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

9

Strana od-do

"2886-1"-"2886-9"

Kód UT WoS článku

000948038400001

EID výsledku v databázi Scopus

2-s2.0-85150197899