New-Generation Heterocyclic Bis-Pentamethinium Salts as
Potential Cytostatic Drugs with Dual IL-6R and
Mitochondria-Targeting Activity

J 2022

New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity

TALIANOVÁ, Veronika; Zdeněk KEJÍK; Robert KAPLÁNEK; Kateřina VESELÁ; Nikita ABRAMENKO et al.

Základní údaje

Originální název

New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity

Autoři

Vydání

Pharmaceutics, Basel, MDPI, 2022, 1999-4923

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.400

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/22:00126561

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

IL-6R synthetic inhibitors; mitochondria; cancer

Štítky

14110515, 14110518, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 2. 2023 14:04, Mgr. Tereza Miškechová

Anotace

V originále

IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding −9.5 and −8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.

Návaznosti

LM2018133, projekt VaV

Název: Český národní uzel Evropské infrastruktury pro translační medicínu (Akronym: EATRIS-ERIC-CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Involvement of Czech Translational Medicine Infrastructure to the European Advanced Translational Research Infrastructure in Medicine

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

NU21-08-00407, projekt VaV

Název: Funkční nanoroboti pro navigovanou kombinovanou nádorovou terapii

Investor: Ministerstvo zdravotnictví ČR, Funkční nanoroboti pro navigovanou kombinovanou nádorovou terapii, Podprogram 1 - standardní

TN01000013, projekt VaV

Název: Personalizovaná medicína - diagnostika a terapie

Investor: Technologická agentura ČR, Personalizovaná medicína - diagnostika a terapie

Přiložené soubory

New-Generation_Heterocyclic_Bis-Pentamethinium_Salts_as_Potential_Cytostatic_Drugs_with_Dual_IL-6R_and_Mitochondria-Targeting_Activity.pdf

Citovat

TALIANOVÁ, Veronika; Zdeněk KEJÍK; Robert KAPLÁNEK; Kateřina VESELÁ; Nikita ABRAMENKO; Lukáš LACINA; Karolína STRNADOVÁ; Barbora DVOŘÁNKOVÁ; Pavel MARTÁSEK; Michal MASAŘÍK; Magdalena MEGOVÁ HOUDOVÁ; Petr BUŠEK; Jana KŘÍŽOVÁ; Lucie ZDRAŽILOVÁ; Hana HANSÍKOVÁ; Erik VLČÁK; Vlada FILIMONENKO; Aleksi ŠEDO; Karel SMETANA JR. a Milan JAKUBEK. New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity. Pharmaceutics. Basel: MDPI, 2022, roč. 14, č. 8, s. 1-20. ISSN 1999-4923. Dostupné z: https://doi.org/10.3390/pharmaceutics14081712.

@article{2214527,
   author = {Talianová, Veronika and Kejík, Zdeněk and Kaplánek, Robert and Veselá, Kateřina and Abramenko, Nikita and Lacina, Lukáš and Strnadová, Karolína and Dvořánková, Barbora and Martásek, Pavel and Masařík, Michal and Megová Houdová, Magdalena and Bušek, Petr and Křížová, Jana and Zdražilová, Lucie and Hansíková, Hana and Vlčák, Erik and Filimonenko, Vlada and Šedo, Aleksi and Smetana Jr., Karel and Jakubek, Milan},
   article_location = {Basel},
   article_number = {8},
   doi = {https://doi.org/10.3390/pharmaceutics14081712},
   keywords = {IL-6R synthetic inhibitors; mitochondria; cancer},
   language = {eng},
   issn = {1999-4923},
   journal = {Pharmaceutics},
   title = {New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity},
   url = {https://www.mdpi.com/1999-4923/14/8/1712},
   volume = {14},
   year = {2022}
}

TY  - JOUR
ID  - 2214527
AU  - Talianová, Veronika - Kejík, Zdeněk - Kaplánek, Robert - Veselá, Kateřina - Abramenko, Nikita - Lacina, Lukáš - Strnadová, Karolína - Dvořánková, Barbora - Martásek, Pavel - Masařík, Michal - Megová Houdová, Magdalena - Bušek, Petr - Křížová, Jana - Zdražilová, Lucie - Hansíková, Hana - Vlčák, Erik - Filimonenko, Vlada - Šedo, Aleksi - Smetana Jr., Karel - Jakubek, Milan
PY  - 2022
TI  - New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity
JF  - Pharmaceutics
VL  - 14
IS  - 8
SP  - 1-20
EP  - 1-20
PB  - MDPI
SN  - 19994923
KW  - IL-6R synthetic inhibitors
KW  - mitochondria
KW  - cancer
UR  - https://www.mdpi.com/1999-4923/14/8/1712
N2  - IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding −9.5 and −8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.
ER  -

TALIANOVÁ, Veronika; Zdeněk KEJÍK; Robert KAPLÁNEK; Kateřina VESELÁ; Nikita ABRAMENKO; Lukáš LACINA; Karolína STRNADOVÁ; Barbora DVOŘÁNKOVÁ; Pavel MARTÁSEK; Michal MASAŘÍK; Magdalena MEGOVÁ HOUDOVÁ; Petr BUŠEK; Jana KŘÍŽOVÁ; Lucie ZDRAŽILOVÁ; Hana HANSÍKOVÁ; Erik VLČÁK; Vlada FILIMONENKO; Aleksi ŠEDO; Karel SMETANA JR. a Milan JAKUBEK. New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity. \textit{Pharmaceutics}. Basel: MDPI, 2022, roč.~14, č.~8, s.~1-20. ISSN~1999-4923. Dostupné z: https://doi.org/10.3390/pharmaceutics14081712.

Přehled o publikaci