Chalcogen Bonding (ChB) as a Robust Supramolecular Recognition Motif of Benzisothiazolinone Antibacterials.

1,2-benzisothiazol-3(2H)-one derivatives are highly active against a broad spectrum of fungi as well as Gram positive and Gram negative bacteria. For this reason they are extensively used, for example, as additives in detergents, leather products, paper coatings, and antifouling paintings. In this paper experimental findings are reported proving that the sulfur atom of benzisothiazolinones have a remarkable tendency to form short and directional chalcogen bondings on the extension of the covalent N-S bond and, to a lesser extent, of the C-S bond. Analyses of the Cambridge Structural Database confirm the interaction as a primary recognition motif of these systems. The electrophilicity of sulfur is crucial in the chemical reactions initiating the cascade of events resulting in the biopharmacological activities of benzisothiazolinones. The reported results suggest that the electrophility of sulfur may play a role also at earlier stages than the reactive ones, namely it may pin the compounds at the active site of target enzymes via chalcogen bondings that preorganize the system in the conformation required for the bonds formation/cleavage determining the biopharmacological activity.

Structure-Activity Studies Reveal Scope for Optimisation of Ebselen-Type Inhibition of SARS-CoV-2 Main Protease.

The reactive organoselenium compound ebselen is being investigated for treatment of coronavirus disease 2019 (COVID-19) and other diseases. We report structure-activity studies on sulfur analogues of ebselen with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro ), employing turnover and protein-observed mass spectrometry-based assays. The results reveal scope for optimisation of ebselen/ebselen derivative- mediated inhibition of Mpro , particularly with respect to improved selectivity.

Ebsulfur and Ebselen as highly potent scaffolds for the development of potential SARS-CoV-2 antivirals.

The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (Mpro) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 Mpro by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC50) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074-0.91 µM. Notably, the molecules containing furane substituent displayed higher inhibition against Mpro, followed by Ebselen 1i (IC50 = 0.074 µM) and Ebsulfur 2k (IC50 = 0.11 µM). The action mechanism of 1i and 2k were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to Mpro, while molecular docking suggested that 2k formed an SS bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of Mpro to combat COVID-19.

Review of the Syntheses and Activities of Some Sulfur-Containing Drugs.

BACKGROUND: Sulfur-containing compounds represent an important class of chemical compounds due to their wide range of biological and pharmaceutical properties. Moreover, sulfur-containing compounds may be applied in other fields, such as biological, organic, and materials chemistry. Several studies on the activities of sulfur compounds have already proven their anti-inflammatory properties and use to treat diseases, such as Alzheimer's, Parkinson's, and HIV. Moreover, examples of sulfur-containing compounds include dapsone, quetiapine, penicillin, probucol, and nelfinavir, which are important drugs with known activities. OBJECTIVE: This review will focus on the synthesis and application of some sulfur-containing compounds used to treat several diseases, as well as promising new drug candidates. CONCLUSION: Due to the variety of compounds containing C-S bonds, we have reviewed the different synthetic routes used toward the synthesis of sulfur-containing drugs and other compounds.