Co‐Culture Based Screening Revealed Selective Cytostatic Effects of Pyrazol‐Azepinoindoles

Skvortsov, D.; Zhirkina, I.; Ipatova, D.; Vasilyeva, L.; Ivanenkov, Y.; Rubtsova, M.; Kartsev, V.; Sergiev, P.; Dontsova, O.

Авторы: Skvortsov Dmitry, Zhirkina Irina, Ipatova Daria, Vasilyeva Lilya, Ivanenkov Yan, Rubtsova Maria, Kartsev Victor, Sergiev Petr, Dontsova Olga
Журнал: ChemMedChem
Год издания: 2025
Издательство: Wiley - V C H Verlag GmbbH & Co.
Местоположение издательства: Germany
DOI: 10.1002/cmdc.202500052
Аннотация: This work focuses on the search for new small molecules for anticancer therapy using theFluorescent Cells Co-Cultivation Test (FCCT). This method allows the control of the specificity of the actionof compounds from the earliest stages of drug development. For the FCCT, labelled MCF7' breast cancercells and non-cancerous breast MCF10A cells were co-cultured.Screening of 2025 compounds in the above system and previously developed co-culture of A549'with VA-13 yielded 16 selectively cytotoxic molecules. The results were confirmed by MTT assay for 7 ofthese molecules. Few are known as potential antitumor agents: angelicin, coumarin, and colchicinederivatives. However, the structures of macrocycle 1, pyrazole-azepinoindole derivative 2, and complexheterocyclic derivative 3 were not described as anticancer compounds according to the PubChem andSciFinder databases.Structure-activity relationships were investigated for 2, and its derivatives. The indole with acaprolactam ring (tetrahydro-azepinoindolone core) together with the pyrazolyl at the 3-position are thekey elements of the pharmacophore. The optimized pyrazole-azepinoindole derivative 23 showed SI=18for HCT116 vs VA-13 on the expanded array of cell lines. Its effect is mainly mediated by the G1 arrest ofthe cell cycle.
Добавил в систему: Скворцов Дмитрий Александрович

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Co‐Culture Based Screening Revealed Selective Cytostatic Effects of Pyrazol‐Azepinoindolesстатья

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