Synthesis and Biological Evaluation of Chalconesulfonamides: En Route to Proapoptotic Agents with Antiestrogenic Potency.

Autor: Krymov SK; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia., Salnikova DI; Department of Experimental Tumor Biology, Blokhin N. N. National Medical Research Center of Oncology, Kashirskoe sh. 24, 115522 Moscow, Russia., Dezhenkova LG; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia., Bogdanov FB; Department of Experimental Tumor Biology, Blokhin N. N. National Medical Research Center of Oncology, Kashirskoe sh. 24, 115522 Moscow, Russia., Korlyukov AA; A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Str. 28, 119334 Moscow, Russia., Scherbakov AM; Department of Experimental Tumor Biology, Blokhin N. N. National Medical Research Center of Oncology, Kashirskoe sh. 24, 115522 Moscow, Russia.; Molecular Genetics Laboratory, Institute of Clinical Medicine, National Research Lobachevsky State University of Nizhny Novgorod, Prospekt Gagarina 23, 603950 Nizhny Novgorod, Russia., Shchekotikhin AE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Dec 25; Vol. 17 (1). Date of Electronic Publication: 2023 Dec 25.
DOI: 10.3390/ph17010032
Abstrakt: Breast and other estrogen receptor α-positive cancers tend to develop resistance to existing drugs. Chalcone derivatives possess anticancer activity based on their ability to form covalent bonds with targets acting as Michael acceptors. This study aimed to evaluate the anticancer properties of a series of chalcones ( 7a - l ) with a sulfonamide group attached to the vinyl ketone moiety. Chalconesulfonamides showed a potent antiproliferative effect at low micromolar concentrations against several cancer cell lines, including ERα-positive 4-hydroxytamoxifen-resistant MCF7/HT2. Immunoblotting of samples treated with the lead compound 7e revealed its potent antiestrogenic activity (ERα/GREB1 axis) and induction of PARP cleavage (an apoptosis marker) in breast cancer cells. The obtained compounds represent a promising basis for further development of targeted drugs blocking hormone pathways in cancer cells.
Databáze: MEDLINE
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