Anti-Cancer and Electrochemical Properties of Thiogenistein—New Biologically Active Compound

Abstract

Pharmacological and nutraceutical effects of isoflavones, which include genistein (GE), are attributed to their antioxidant activity protecting cells against carcinogenesis. The knowledge of the oxidation mechanisms of an active substance is crucial to determine its pharmacological properties. The aim of the present work was to explain complex oxidation processes that have been simulated during voltammetric experiments for our new thiolated genistein analog (TGE) that formed the self-assembled monolayer (SAM) on the gold electrode. The thiol linker assured a strong interaction of sulfur nucleophiles with the gold surface. The research comprised of the study of TGE oxidative properties, IR-ATR, and MALDI-TOF measurements of SAM before and after electrochemical oxidation. TGE has been shown to be electrochemically active. It undergoes one irreversible oxidation reaction and one quasi-reversible oxidation reaction in PBS buffer at pH 7.4.. The oxidation of TGE results in electroactive products composed likely from TGE conjugates (e.g., trimers) as part of polymer. The electroactive centers of TGE and its oxidation mechanism were discussed using IR supported by quantum chemical and molecular mechanics calculations. Preliminary in-vitro studies indicate that TGE exhibits higher cytotoxic activity towards DU145 human prostate cancer cells and is safer for normal prostate epithelial cells (PNT2) than genistein itself.

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

“…Additionally, it was confirmed that the potency of the antitumor activity of genistein and its derivatives varies in different tumor types, depending on their selectivity for the target molecules. Our previous studies have shown that the substitution of the -OH group at position seven of the A ring by an ethyl linker and a thioglycolic acid residue allows us to obtain a derivative showing a higher cytotoxic activity against human prostate cancer DU145 cells, but also a lower toxicity against normal prostate epithelial cells (PNT2) compared to its precursor–genistein [ 20 ]. Based on previous promising results, our research has been extended to include two breast cancer lines: the estrogen-positive MCF-7 and the estrogen-negative MDA-MB-231.…”

“…In vitro studies would suggest that changing the hydroxyl for an ether containing an –SH group on the C7 carbon in the A ring may increase the cytotoxic properties of TGE. This effect can be attributed to the presence of a highly reactive -SH group [ 20 , 28 ]. Marik and coworkers also proved that the substitution of the -OH group at position seven of the A ring by aliphatic chains and heterocyclic 1,2,3-triazole moieties enhances the cytotoxic properties.…”

“…The band from the carbonyl stretching vibration from the chain [ 20 ] has the same value of 1738 cm −1 before and after oxidation. However, the band from the carbonyl stretching vibration assigned to the ring [ 20 ] is shifted towards higher wavenumbers from 1659 to 1667 cm −1 , which indicates a weakening or breaking of the intramolecular C=O–O-H hydrogen bond.…”

“…To summarize, this work becomes a continuation of our former study on physicochemical, biological, and theoretical properties of a new compound, TGE [ 20 ]. Here, we estimated the oxidation with electrochemical and chemical (H 2 O 2 ) methods by identifying the main oxidation products with MS/MS spectrometry and IR spectroscopy, antitumor and antioxidant properties by biological methods, and by theoretical modeling predicting antioxidant activity.…”

Novel Strategies in the Development of New Therapies, Drug Substances, and Drug Carriers Volume I

“…The pharmacological actions of isoflavones of natural origin, such as genistein (GE), relate to their antioxidant activity, and they protect cells from carcinogenesis. Using a self-assembled monolayer on the gold electrode in simulated voltammetry, Stolarczyk et al [ 3 ] have revealed that a new thiolated genistein analog (TGE) has antioxidant activity. The electroactive centers of TGE and its oxidation mechanism have been elucidated using infrared spectrometry supported by quantum chemical and molecular mechanics calculations.…”