Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells.
| Title: | Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells. |
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| Authors: | Neganova ME; Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russia.; Aleksandrova YR; Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russia.; Sharova EV; Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russia.; Smirnova EV; Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russia.; Artyushin OI; Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russia.; Nikolaeva NS; Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Semakov AV; Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Schagina IA; Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Akylbekov N; Laboratory of Engineering Profile 'Physical and Chemical Methods of Analysis', Korkyt Ata Kyzylorda University, Aiteke bi Str. 29A, 120014 Kyzylorda, Kazakhstan.; Kurmanbayev R; Laboratory of Engineering Profile 'Physical and Chemical Methods of Analysis', Korkyt Ata Kyzylorda University, Aiteke bi Str. 29A, 120014 Kyzylorda, Kazakhstan.; Orynbekov D; Laboratory of Engineering Profile 'Physical and Chemical Methods of Analysis', Korkyt Ata Kyzylorda University, Aiteke bi Str. 29A, 120014 Kyzylorda, Kazakhstan.; Brel VK; Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russia. |
| Source: | Molecules (Basel, Switzerland) [Molecules] 2024 Jun 11; Vol. 29 (12). Date of Electronic Publication: 2024 Jun 11. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, c1995- |
| MeSH Terms: | Sesquiterpenes*/pharmacology ; Sesquiterpenes*/chemistry ; Lactones*/chemistry ; Lactones*/pharmacology ; Lactones*/chemical synthesis ; Antineoplastic Agents*/pharmacology ; Antineoplastic Agents*/chemistry ; Antineoplastic Agents*/chemical synthesis ; Piperidones*/pharmacology ; Piperidones*/chemistry; Glycolysis/drug effects ; Cell Proliferation/drug effects ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Humans ; Cell Line, Tumor ; Molecular Docking Simulation ; Drug Screening Assays, Antitumor |
| Abstract: | 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. |
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| Grant Information: | the Non-Profit Joint-Stock Company "Korkyt Ata Kyzylorda University" the Non-Profit Joint-Stock Company "Korkyt Ata Kyzylorda University" |
| Contributed Indexing: | Keywords: 3,5-bis(arylidene)-4-piperidone; acetylenes; alantolactone; azides; click chemistry; cytotoxicity; dehydrocostuslactone; glycolysis; sesquiterpene lactones |
| Substance Nomenclature: | 0 (Sesquiterpenes); 0 (Lactones); 0 (Antineoplastic Agents); 0 (Piperidones) |
| Entry Date(s): | Date Created: 20240627 Date Completed: 20240627 Latest Revision: 20240629 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11207066 |
| DOI: | 10.3390/molecules29122765 |
| PMID: | 38930831 |
| Database: | MEDLINE |
Journal Article