Discovery of a Highly Promising Disulfide Derivative Scaffold as Inhibitor of SARS-CoV-2 Main Protease.

The main protease (M) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of M inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1 a-h), dithiocarbamate-Cu(II) complexes (2 a-hCu) and disulfide derivatives (2 a-e, 2 i) as potent inhibitors of M, with IC value range of 0.

A dual covalent binder for labelling and inhibiting serine and metallo-carbapenemases.

The continuous emergence of multi-drug resistant pathogens co-expressing serine and metallo-carbapenemases seriously threatens the efficacy of carbapenem. Here, we report the first SeCN-derived dual inhibitor of serine and metallo-carbapenemases with IC values ranging from 0.0038 to 1.

Dihydroxyphenyl-substituted thiosemicarbazone: A potent scaffold for the development of metallo-β-lactamases inhibitors and antimicrobial.

The superbug infection mediated by metallo-β-lactamases (MβLs) has grown into anemergent health threat, and development of MβL inhibitors is an ideal strategy to combat the infection. In this work, twenty-five thiosemicarbazones 1a-e, 2a-e, 3a-e, 4a-d, 5a-d and 6a-b were synthesized and assayed against MβLs ImiS, NDM-1 and L1. The gained molecules specifically inhibited NDM-1 and ImiS, exhibiting an IC value in the range of 0.

Hydroxamate and thiosemicarbazone: Two highly promising scaffolds for the development of SARS-CoV-2 antivirals.

The emerging COVID-19 pandemic generated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has severely threatened human health. The main protease (M) of SARS-CoV-2 is promising target for antiviral drugs, which plays a vital role for viral duplication. Development of the inhibitor against M is an ideal strategy to combat COVID-19.

Quinolinyl sulfonamides and sulphonyl esters exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1).

The "superbug" infection caused by metallo-β-lactamases (MβLs) has grown into anemergent health threat, and development of effective MβL inhibitors to restore existing antibiotic efficacy is an ideal alternative. Although the serine-β-lactamase inhibitors have been used in clinical settings, MβL inhibitors are not available to date. In this work, thirty-one quinolinyl sulfonamides 1a-p and sulphonyl esters 2a-o were synthesized and assayed against MβL NDM-1.

Hydroxamates as a potent skeleton for the development of metallo-β-lactamase inhibitors.

Bacterial resistance caused by metallo-β-lactamases (MβLs) has become an emerging public health threat, and the development of MβLs inhibitor is an effective way to overcome the resistance. In this study, thirteen novel O-aryloxycarbonyl hydroxamates were constructed and assayed against MβLs. The obtained molecules specifically inhibited imipenemase-1 (IMP-1) and New Delhi metallo-β-lactamase-1, exhibiting an IC value in the range of 0.

N-acylhydrazones confer inhibitory efficacy against New Delhi metallo-β-lactamase-1.

The expression of β-lactamases, especially metallo-β-lactamases (MβLs) in bacteria is one of the main causes of drug resistance. In this work, an effective N-acylhydrazone scaffold as MβL inhibitor was constructed and characterized. The biological activity assays indicated that the synthesized N-acylhydrazones 1-11 preferentially inhibited MβL NDM-1, and 1 was found to be the most effective inhibitor with an IC of 1.