UDC

616-006.6:57.085.2

DOI

10.37482/2687-1491-Z227

Authors

Irina V. Mezhevova* ORCID: https://orcid.org/0000-0002-7902-7278
Svetlana Yu. Filippova* ORCID: https://orcid.org/0000-0002-4558-5896
Tatiana V. Chembarova* ORCID: https://orcid.org/0000-0002-4555-8556
Nadezhda V. Gnennaya* ORCID: https://orcid.org/0000-0002-3691-3317
Inna A. Novikova* ORCID: https://orcid.org/0000-0002-6496-9641
Anna S. Goncharova* ORCID: https://orcid.org/0000-0003-0676-0871
Yurii A. Sayapin** ORCID: https://orcid.org/0000-0002-3180-1762
Evgeniy A. Gusakov*** ORCID: https://orcid.org/0000-0001-7593-1334
Inna O. Tupaeva*** ORCID: https://orcid.org/0000-0002-7695-9512

Abstract

Organic synthesis is a valuable source of promising antitumour drugs. The purpose of this paper was to study the cytotoxic effect of a new tropolone derivative 2-(1,1-dimethyl-1H-benzo[e]indolin-2-yl)-5,6, 7-trichloro-1,3-tropolone (JO-122) on the SW620 colon cancer cell line, compared with the standard chemotherapy drug 5-fluorouracil. Materials and methods. The research was conducted on a permanent colon adenocarcinoma cell line SW620. Cytotoxic activity of JO-122 was determined in an experiment with the construction of a dose– response curve; the number of living cells was measured indirectly using the MTT assay. The half inhibitory concentration (IC50) of the substance was further validated in the trypan blue test. Apoptosis in the SW620 cell culture was studied by assessing the morphological changes in cell nuclei stained with Hoechst 33342. Results. IC50 for JO-122 was 0.27 ± 0.07 mmol/l, which is almost 10 times less than for 5-fluorouracil (IC50(5-FU) = = 23.5 ± 3.5 mmol/l). In the trypan blue test, for a dose of 0.27 mmol/l we found a decrease in the number of living cells by 35 ± 7.2 %, while the proportion of dead cells was 12 ± 3.2 %. We assume that the mechanism of action of JO-122 on the SW620 culture is associated with a cell cycle arrest in the G0/G1 phase without the induction of apoptosis, which leads to a decrease in the proliferative activity of cells in the tested culture. Further studies are required to establish the mechanism of action of JO-122 on malignant cells.

Keywords

tropolone derivatives, colon cancer, SW620, new antitumour agents, anticancer chemotherapy, JO-122

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