Synthesis and cytotoxic activity of 1,5,6,7-tetrahydroindol-4-one derivatives and its thio analogue

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Derivatives of 1,5,6,7-tetrahydroindol-4-one and its thio analogue were synthesized and their cytotoxicity against HEK293, Jurkat and MCF-7 cells was investigated in vitro. The hit compound, 6,6-dimethyl-1-(2-methylphenyl)-2-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one, was found to inhibit the metabolic activity of lymphoblastic leukemia cells (Jurkat) with IC50 = 14.8 µM and normal human embryonic kidney cells (HEK293) with IC50 = 93.63 µM. The proposed mechanism of cytotoxic action of the most active compound was shown in silico to be mediated by interaction with the cyclin-dependent kinase CDK9 site.

Толық мәтін

Рұқсат жабық

Авторлар туралы

V. Sorokina

Ufa Federal Research Center of the Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: tsypysheva.ip@gmail.com
ORCID iD: 0000-0001-5311-9580

Ufa Institute of Chemistry

Ресей, Ufa

D. Tsypyshev

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID iD: 0000-0003-4551-0226

Ufa Institute of Chemistry

Ресей, Ufa

A. Koval’skaya

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID iD: 0000-0001-7772-2894

Ufa Institute of Chemistry

Ресей, Ufa

V. Vakhitov

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID iD: 0000-0001-8805-9872

Institute of Biochemistry and Genetics

Ресей, Ufa

I. Tsypysheva

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID iD: 0000-0002-5025-8742

Institute of Biochemistry and Genetics

Ресей, Ufa

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2. Fig. 1. Evaluation of the effect of compound 3 on cell cycle progression of HEK293, MCF-7, and Jurkat cells. Cells with the test compound at the IC50 concentration determined for each cell line were incubated for 24 (a), 48 (b), 72 hours (c). Data obtained from two independent experiments (N = 2, n = 6) are presented as mean ± standard deviation; * – p < 0.05 (Wilcoxon t-test).

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3. Fig.2. Docking poses of derivative 3 (a) and reference ligand S-CR8 (b) at the 3LQ5 CDK9 binding site; hydrogen bonds are indicated by dotted lines.

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4. Scheme 1.

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5. Scheme 2.

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6. Scheme 3.

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