Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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 изданиях › статья › Рецензирование
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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