10.1021/jm070669h
The research focuses on the synthesis and evaluation of a chemical library of inhibitors targeting Mycobacterium tuberculosis mycothiol-associated enzymes, specifically GlcNAc-Ins deacetylase (MshB) and mycothiol-S-conjugate amidase (MCA). The purpose of this study was to develop small molecules that could interfere with mycothiol (MSH) biosynthesis or MSH-assisted detoxification, which could potentially serve as new antitubercular agents. The researchers synthesized a series of inhibitors based on natural product structures known to competitively inhibit MCA. The library of inhibitors was biased to include structural features of these natural products, and molecular docking studies were used to predict their binding modes within the active sites of the target enzymes. The study concluded that the synthesized inhibitors were the first reported to target MshB and supported the potential of natural product-substrate chimeras to act as dual inhibitors for both MshB and MCA. Key chemicals used in the synthesis process included 1-myo-D-inositol (myo-D-Ins), glucosamine (GlcN), N-acetyl-cysteine, and various sulfonyl chlorides, phosphonates, and other organic compounds to construct the desired inhibitor scaffolds and evaluate their biological activity.
10.1124/jpet.120.000266
The research aims to investigate the mechanism by which a novel chemical compound, SF-3-030, selectively targets and inhibits the proliferation of melanoma cells with constitutively active ERK1/2 signaling, such as those harboring the BRAF V600E mutation. The study reveals that SF-3-030 interacts with ERK2, forming a covalent adduct on cysteine 252, which is near the docking site for substrate recruitment. This interaction leads to rapid changes in immediate early gene levels, particularly those containing the DEF motif, and induces an oxidative stress response, which is associated with the inhibition of melanoma cell proliferation. The research concludes that SF-3-030's mechanism of action is ROS-dependent but independent of NRF2, suggesting a potential therapeutic approach for melanoma treatment. Key chemicals used in the study include SF-3-030, ERK2, and various ROS inhibitors such as N-acetyl cysteine (NAC), sodium pyruvate, and mannitol.
10.1021/jo902226t
The study focuses on the synthesis and evaluation of 3-pyridinols, which are compounds carrying alkyltelluro, alkylseleno, and alkylthio groups, as potent antioxidant agents. These pyridinols were tested for their ability to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system and in a homogeneous phase. The chemicals used in the study include various 3-pyridinols with different substituents, N-acetylcysteine (NAC) as a water-soluble co-antioxidant, and N-tert-butoxycarbonyl cysteine methyl ester (LipCys), a lipid-soluble analogue of NAC. The purpose of these chemicals was to assess their antioxidant activity, specifically their capacity to quench peroxyl radicals, regenerate through reduction by thiol reducing agents, and their potential catalytic antioxidant behavior. The study aimed to understand the kinetic, thermodynamic, and mechanistic aspects of these antioxidants' activities and to identify the structural features that contribute to their high reactivity and effectiveness.
