Abstract
Electrochemical methods are powerful in the characterization and design of redox-modulating agents. We, herein, report the electrochemical investigation, in aprotic medium, of eleven synthetic 3-thio-substituted-nor-beta-lapachones, along with the determination of cytotoxic activity and correspondent selectivity index, against several cancer cell lines and one normal cell. Four of the quinones are novel compounds. The redox behavior is representative of two independent systems: the easy reduction of the quinone moiety and, at far more negative potential, the reductive cleavage of the C-S-C bonding; and the anodic part controlled by the oxidation of the sulfur moiety. The compounds have shown relevant cytotoxic activity, with emphasis on 3-phenyl-thio-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione (compound 2), which mechanism of molecular action was shown to be related to reactive oxygen species (ROS) release. Despite the absence of a linear correlation, there is a trend: the majority of the thionaphthoquinones, with values of first wave reduction potential, less negative than -0.65 V, were active. The less electrophilic compound (3-(cyclohexylthio)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione, cyclohexyl derivative) is also the less cytotoxic toward cancer cells. Agents containing chalcogens and quinones can be used to attack entities with a disturbed redox balance.
Highlights
Redox processes, central to life, pervade practically all fundamental bioprocesses, from bioenergetics to metabolism and life functions.[1]A disturbed intracellular redox balance, resulting in oxidative stress (OS), has been considered as the biochemical basis for various human diseases, including different types of cancer.[2,3] OS is an imbalance between oxidants, mainly reactive oxygen species (ROS), and antioxidants, in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage.[1,2]Vol 30, No 3, 2019 de Paiva et al.Some cancer cells proliferate under conditions of high-intensity OS,[1] compared with normal cells, because of their accelerated metabolism
A red solid precipitate of the cationic ortho-quinone methide (o-QM) intermediate immediately formed was reacted with R−SH compound, resulting in a red solid, which was purified by flash column chromatography on silica gel (Figure 2)
The structures of the synthesized compounds were confirmed by spectroscopic techniques, such as 1H and 13C nuclear magnetic resonance (NMR), infrared spectroscopy and High-resolution mass spectra (HRMS)-ESI
Summary
Central to life, pervade practically all fundamental bioprocesses, from bioenergetics to metabolism and life functions.[1]A disturbed intracellular redox balance, resulting in oxidative stress (OS), has been considered as the biochemical basis for various human diseases, including different types of cancer.[2,3] OS is an imbalance between oxidants, mainly reactive oxygen species (ROS), and antioxidants, in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage.[1,2]Vol 30, No 3, 2019 de Paiva et al.Some cancer cells proliferate under conditions of high-intensity OS,[1] compared with normal cells, because of their accelerated metabolism. A disturbed intracellular redox balance, resulting in oxidative stress (OS), has been considered as the biochemical basis for various human diseases, including different types of cancer.[2,3] OS is an imbalance between oxidants, mainly reactive oxygen species (ROS), and antioxidants, in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage.[1,2]. Compared to non-cancerous cells, ROS levels are considerably closer to the critical redox threshold at which cell death is induced.[4,5,6] Normal cells often can tolerate a certain level of exogenous ROS, whereas cancer cells cannot.[7] These pre-existing biochemical differences between healthy and malignant tissues are significant and are used in the design of selective redox chemotherapeutic drugs.[6,7,8,9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
