Thiogenistein-Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products.

Autor: Stolarczyk EU; Analytical Department, Łukasiewicz Research Network-Industrial Chemistry Institute, 8 Rydygiera Street, 01-793 Warsaw, Poland., Strzempek W; Faculty of Chemistry, Jagiellonian University, 2 Gronostajowa Str., 30-387 Krakow, Poland.; Faculty of Pharmacy, Collegium Medicum, Jagiellonian University, 9 Medyczna Str., 30-068 Krakow, Poland., Łaszcz M; Analytical Department, Łukasiewicz Research Network-Industrial Chemistry Institute, 8 Rydygiera Street, 01-793 Warsaw, Poland.; Department of Falsified Medicines and Medical Devices, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland., Leś A; Faculty of Chemistry, University of Warsaw, 1 Pasteura Street, 02-093 Warsaw, Poland., Menaszek E; Faculty of Pharmacy, Collegium Medicum, Jagiellonian University, 9 Medyczna Str., 30-068 Krakow, Poland., Stolarczyk K; Faculty of Chemistry, University of Warsaw, 1 Pasteura Street, 02-093 Warsaw, Poland.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Jul 15; Vol. 23 (14). Date of Electronic Publication: 2022 Jul 15.
DOI: 10.3390/ijms23147816
Abstrakt: Isoflavonoids such as genistein (GE) are well known antioxidants. The predictive biological activity of structurally new compounds such as thiogenistein (TGE)-a new analogue of GE-becomes an interesting way to design new drug candidates with promising properties. Two oxidation strategies were used to characterize TGE oxidation products: the first in solution and the second on the 2D surface of the Au electrode as a self-assembling TGE monolayer. The structure elucidation of products generated by different oxidation strategies was performed. The electrospray ionization mass spectrometry (ESI-MS) was used for identifying the product of electrochemical and hydrogen peroxide oxidation in the solution. Fourier transform infrared spectroscopy (FT-IR) with the ATR mode was used to identify a product after hydrogen peroxide treatment of TGE on the 2D surface. The density functional theory was used to support the experimental results for the estimation of antioxidant activity of TGE as well as for the molecular modeling of oxidation products. The biological studies were performed simultaneously to assess the suitability of TGE for antioxidant and antitumor properties. It was found that TGE was characterized by a high cytotoxic activity toward human breast cancer cells. The research was also carried out on mice macrophages, disclosing that TGE neutralized the production of the LPS-induced reactive oxygen species (ROS) and exhibits ABTS (2,2'-azino-bis-3-(ethylbenzothiazoline-6-sulphonic acid) radical scavenging ability. In the presented study, we identified the main oxidation products of TGE generated under different environmental conditions. The electroactive centers of TGE were identified and its oxidation mechanisms were proposed. TGE redox properties can be related to its various pharmacological activities. Our new thiolated analogue of genistein neutralizes the LPS-induced ROS production better than GE. Additionally, TGE shows a high cytotoxic activity against human breast cancer cells. The viability of MCF-7 (estrogen-positive cells) drops two times after a 72-h incubation with 12.5 μM TGE (viability 53.86%) compared to genistein (viability 94.46%).
Databáze: MEDLINE
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