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Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity. / Krasavin, Mikhail; Sharonova, Tatiana; Sharoyko, Vladimir; Zhukovsky, Daniil; Kalinin, Stanislav; Žalubovskis, Raivis; Tennikova, Tatiana; Supuran, Claudiu T.

в: Journal of Enzyme Inhibition and Medicinal Chemistry, Том 35, № 1, 2020, стр. 665-671.

Результаты исследований: Научные публикации в периодических изданияхстатьяРецензирование

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@article{212b022fd46f4330bedc05175169cf35,
title = "Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity",
abstract = "A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell{\textquoteright}s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.",
keywords = "Anticancer agents, cancer cell defence mechanisms, carbonic anhydrase inhibition, dual pharmacophores, hypoxia, Michael acceptors, oxidative stress, synergistic effect, thioredoxin reductase inhibition, zinc-binding group, Humans, Structure-Activity Relationship, Cell Survival/drug effects, Thioredoxin-Disulfide Reductase/antagonists & inhibitors, Antineoplastic Agents/chemical synthesis, Dose-Response Relationship, Drug, Cell Line, Tumor, Carbonic Anhydrases/metabolism, Molecular Structure, Sulfonamides/chemical synthesis, Cell Proliferation/drug effects, Enzyme Inhibitors/chemical synthesis, Drug Screening Assays, Antitumor, SYSTEM, DESIGN, PERIPHERY",
author = "Mikhail Krasavin and Tatiana Sharonova and Vladimir Sharoyko and Daniil Zhukovsky and Stanislav Kalinin and Raivis {\v Z}alubovskis and Tatiana Tennikova and Supuran, {Claudiu T.}",
year = "2020",
doi = "10.1080/14756366.2020.1734800",
language = "English",
volume = "35",
pages = "665--671",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
issn = "1475-6366",
publisher = "Taylor & Francis",
number = "1",

}

RIS

TY - JOUR

T1 - Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity

AU - Krasavin, Mikhail

AU - Sharonova, Tatiana

AU - Sharoyko, Vladimir

AU - Zhukovsky, Daniil

AU - Kalinin, Stanislav

AU - Žalubovskis, Raivis

AU - Tennikova, Tatiana

AU - Supuran, Claudiu T.

PY - 2020

Y1 - 2020

N2 - A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell’s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.

AB - A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell’s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.

KW - Anticancer agents

KW - cancer cell defence mechanisms

KW - carbonic anhydrase inhibition

KW - dual pharmacophores

KW - hypoxia

KW - Michael acceptors

KW - oxidative stress

KW - synergistic effect

KW - thioredoxin reductase inhibition

KW - zinc-binding group

KW - Humans

KW - Structure-Activity Relationship

KW - Cell Survival/drug effects

KW - Thioredoxin-Disulfide Reductase/antagonists & inhibitors

KW - Antineoplastic Agents/chemical synthesis

KW - Dose-Response Relationship, Drug

KW - Cell Line, Tumor

KW - Carbonic Anhydrases/metabolism

KW - Molecular Structure

KW - Sulfonamides/chemical synthesis

KW - Cell Proliferation/drug effects

KW - Enzyme Inhibitors/chemical synthesis

KW - Drug Screening Assays, Antitumor

KW - SYSTEM

KW - DESIGN

KW - PERIPHERY

UR - http://www.scopus.com/inward/record.url?scp=85081212819&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/d8e083a4-e5d8-3ddf-a911-fb4ab1553d7c/

U2 - 10.1080/14756366.2020.1734800

DO - 10.1080/14756366.2020.1734800

M3 - Article

C2 - 32131646

AN - SCOPUS:85081212819

VL - 35

SP - 665

EP - 671

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

IS - 1

ER -

ID: 52376043