The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers

Sokolov, Mikhail N.; Rozhkov, Vladimir V.; Uspenskaya, Maria E.; Ulchenko, Darya N.; Shmygarev, Vladimir I.; Trukhan, Vladimir M.; Churakov, Andrei V.; Shimanovsky, Nikolay L.; Fedotcheva, Tatiana A.

doi:10.3390/biom14030373

Open AccessArticle

The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers

by

Mikhail N. Sokolov

¹,

Vladimir V. Rozhkov

¹,

Maria E. Uspenskaya

²

,

Darya N. Ulchenko

²

,

Vladimir I. Shmygarev

¹,

Vladimir M. Trukhan

¹

,

Andrei V. Churakov

³

,

Nikolay L. Shimanovsky

² and

Tatiana A. Fedotcheva

^2,*

¹

Institute for Translation Medicine and Biotechnology, Sechenov First Moscow State Medical University, 2 Bolshaya Pirogovskaya St., Bld. 4, Moscow 119435, Russia

²

Laboratory of Molecular Pharmacology, Pirogov Russian National Research Medical University, 1 Ostrovityanova St., Moscow 117997, Russia

³

Kurnakov Institute of General and Inorganic Chemistry, the Russian Academy of Sciences, 31 Leninsky Av., Moscow 119991, Russia

^*

Author to whom correspondence should be addressed.

Biomolecules 2024, 14(3), 373; https://doi.org/10.3390/biom14030373

Submission received: 2 March 2024 / Accepted: 16 March 2024 / Published: 19 March 2024

(This article belongs to the Topic Design, Synthesis and Biological Evaluation of Novel Small Molecules as Multi-target Enzyme Inhibitors)

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Abstract

In order to evaluate the role of substituents at 3-C and 17-C in the cytotoxic and cytoprotective actions of DHEA and 5-AED molecules, their derivatives were synthesized by esterification using the corresponding acid anhydrides or acid chlorides. As a result, seven compounds were obtained: four DHEA derivatives (DHEA 3-propionate, DHEA 3-butanoate, DHEA 3-acetate, DHEA 3-methylsulfonate) and three 5-AED derivatives (5-AED 3-butanoate, 5-AED 3,17-dipropionate, 5-AED 3,17-dibutanoate). All of these compounds showed micromolar cytotoxic activity toward HeLa and K562 human cancer cells. The maximum cytostatic effect during long-term incubation for five days with HeLa and K562 cells was demonstrated by the propionic esters of the steroids: DHEA 3-propionate and 5-AED 3,17-dipropionate. These compounds stimulated the growth of normal Wi-38 cells by 30–50%, which indicates their cytoprotective properties toward noncancerous cells. The synthesized steroid derivatives exhibited antioxidant activity by reducing the production of reactive oxygen species (ROS) by peripheral blood mononuclear cells from healthy volunteers, as demonstrated in a luminol-stimulated chemiluminescence assay. The highest antioxidant effects were shown for the propionate ester of the steroid DHEA. DHEA 3-propionate inhibited luminol-stimulated chemiluminescence by 73% compared to the control, DHEA, which inhibited it only by 15%. These data show the promise of propionic substituents at 3-C and 17-C in steroid molecules for the creation of immunostimulatory and cytoprotective substances with antioxidant properties.

Keywords: dehydroepiandrosterone; androstenediol; DHEA; 5-AED; K562; HeLa; Wi-38; PBMC; luminol-stimulated chemiluminescence

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MDPI and ACS Style

Sokolov, M.N.; Rozhkov, V.V.; Uspenskaya, M.E.; Ulchenko, D.N.; Shmygarev, V.I.; Trukhan, V.M.; Churakov, A.V.; Shimanovsky, N.L.; Fedotcheva, T.A. The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers. Biomolecules 2024, 14, 373. https://doi.org/10.3390/biom14030373

AMA Style

Sokolov MN, Rozhkov VV, Uspenskaya ME, Ulchenko DN, Shmygarev VI, Trukhan VM, Churakov AV, Shimanovsky NL, Fedotcheva TA. The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers. Biomolecules. 2024; 14(3):373. https://doi.org/10.3390/biom14030373

Chicago/Turabian Style

Sokolov, Mikhail N., Vladimir V. Rozhkov, Maria E. Uspenskaya, Darya N. Ulchenko, Vladimir I. Shmygarev, Vladimir M. Trukhan, Andrei V. Churakov, Nikolay L. Shimanovsky, and Tatiana A. Fedotcheva. 2024. "The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers" Biomolecules 14, no. 3: 373. https://doi.org/10.3390/biom14030373

APA Style

Sokolov, M. N., Rozhkov, V. V., Uspenskaya, M. E., Ulchenko, D. N., Shmygarev, V. I., Trukhan, V. M., Churakov, A. V., Shimanovsky, N. L., & Fedotcheva, T. A. (2024). The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers. Biomolecules, 14(3), 373. https://doi.org/10.3390/biom14030373

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The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers

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