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Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells
by
Schagina, I. A.
, Aleksandrova, Yu. R.
, Kurmanbayev, R.
, Artyushin, O. I.
, Orynbekov, D.
, Brel, V. K.
, Smirnova, E. V.
, Sharova, E. V.
, Nikolaeva, N. S.
, Neganova, M. E.
, Akylbekov, N.
, Semakov, A. V.
in
3,5-bis(arylidene)-4-piperidone
/ acetylenes
/ alantolactone
/ Antineoplastic Agents - chemical synthesis
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ azides
/ Brain cancer
/ Breast cancer
/ Cancer
/ Cell cycle
/ Cell Line, Tumor
/ Cell Proliferation - drug effects
/ Chemistry
/ Chromatography
/ Cytotoxicity
/ dehydrocostuslactone
/ Drug Screening Assays, Antitumor
/ Enzymes
/ Genetic aspects
/ Glycolysis - drug effects
/ Humans
/ Kinases
/ Lactones
/ Lactones - chemical synthesis
/ Lactones - chemistry
/ Lactones - pharmacology
/ Ligands
/ Metabolism
/ Metabolites
/ Molecular Docking Simulation
/ Neoplasms - drug therapy
/ Neoplasms - metabolism
/ Neoplasms - pathology
/ Physiological aspects
/ Piperidones - chemistry
/ Piperidones - pharmacology
/ sesquiterpene lactones
/ Sesquiterpenes - chemistry
/ Sesquiterpenes - pharmacology
/ Toxicity
/ Tumors
2024
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Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells
by
Schagina, I. A.
, Aleksandrova, Yu. R.
, Kurmanbayev, R.
, Artyushin, O. I.
, Orynbekov, D.
, Brel, V. K.
, Smirnova, E. V.
, Sharova, E. V.
, Nikolaeva, N. S.
, Neganova, M. E.
, Akylbekov, N.
, Semakov, A. V.
in
3,5-bis(arylidene)-4-piperidone
/ acetylenes
/ alantolactone
/ Antineoplastic Agents - chemical synthesis
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ azides
/ Brain cancer
/ Breast cancer
/ Cancer
/ Cell cycle
/ Cell Line, Tumor
/ Cell Proliferation - drug effects
/ Chemistry
/ Chromatography
/ Cytotoxicity
/ dehydrocostuslactone
/ Drug Screening Assays, Antitumor
/ Enzymes
/ Genetic aspects
/ Glycolysis - drug effects
/ Humans
/ Kinases
/ Lactones
/ Lactones - chemical synthesis
/ Lactones - chemistry
/ Lactones - pharmacology
/ Ligands
/ Metabolism
/ Metabolites
/ Molecular Docking Simulation
/ Neoplasms - drug therapy
/ Neoplasms - metabolism
/ Neoplasms - pathology
/ Physiological aspects
/ Piperidones - chemistry
/ Piperidones - pharmacology
/ sesquiterpene lactones
/ Sesquiterpenes - chemistry
/ Sesquiterpenes - pharmacology
/ Toxicity
/ Tumors
2024
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Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells
by
Schagina, I. A.
, Aleksandrova, Yu. R.
, Kurmanbayev, R.
, Artyushin, O. I.
, Orynbekov, D.
, Brel, V. K.
, Smirnova, E. V.
, Sharova, E. V.
, Nikolaeva, N. S.
, Neganova, M. E.
, Akylbekov, N.
, Semakov, A. V.
in
3,5-bis(arylidene)-4-piperidone
/ acetylenes
/ alantolactone
/ Antineoplastic Agents - chemical synthesis
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ azides
/ Brain cancer
/ Breast cancer
/ Cancer
/ Cell cycle
/ Cell Line, Tumor
/ Cell Proliferation - drug effects
/ Chemistry
/ Chromatography
/ Cytotoxicity
/ dehydrocostuslactone
/ Drug Screening Assays, Antitumor
/ Enzymes
/ Genetic aspects
/ Glycolysis - drug effects
/ Humans
/ Kinases
/ Lactones
/ Lactones - chemical synthesis
/ Lactones - chemistry
/ Lactones - pharmacology
/ Ligands
/ Metabolism
/ Metabolites
/ Molecular Docking Simulation
/ Neoplasms - drug therapy
/ Neoplasms - metabolism
/ Neoplasms - pathology
/ Physiological aspects
/ Piperidones - chemistry
/ Piperidones - pharmacology
/ sesquiterpene lactones
/ Sesquiterpenes - chemistry
/ Sesquiterpenes - pharmacology
/ Toxicity
/ Tumors
2024
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Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells
Journal Article
Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells
2024
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Overview
In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.
Publisher
MDPI AG,MDPI
Subject
3,5-bis(arylidene)-4-piperidone
/ Antineoplastic Agents - chemical synthesis
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ azides
/ Cancer
/ Cell Proliferation - drug effects
/ Drug Screening Assays, Antitumor
/ Enzymes
/ Humans
/ Kinases
/ Lactones
/ Lactones - chemical synthesis
/ Ligands
/ Molecular Docking Simulation
/ Sesquiterpenes - pharmacology
/ Toxicity
/ Tumors
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