Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study

Węglarz-Tomczak, Ewelina; Burda-Grabowska, Małgorzata; Giurg, Mirosław; Mucha, Artur

doi:10.1016/j.bmcl.2016.09.050

Cited by 32 publications

(39 citation statements)

References 45 publications

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“…In this paper, we present inhibitory activity of twelve ebselen derivatives obtained by substitution/functionalization of the phenyl ring towards SARS-CoV-1 PL pro (PL pro SARS) and SARS-CoV-2 PL pro (PL pro CoV2). Previously, these derivatives were proven to be highly effective towards human methionine aminopeptidase 2 [19] and antiviral and antimicrobial agents [20]. We show that some of them indeed possess higher activity than ebselen, that has been recently reported as PL pro CoV2 inhibitor [12], and, thus, could be considered as novel potential drugs against COVID-19.…”

Section: Introductionmentioning

confidence: 67%

Discovery of potent inhibitors of PL^proCoV2 by screening a library of selenium-containing compounds

Węglarz-Tomczak

Tomczak

Giurg

et al. 2020

Preprint

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A collection of twelve organoselenium compounds, structural analogues of antioxidant drug ebselen were screened for inhibition of the papain-like protease (PL pro ) from the acute respiratory syndrome coronavirus 2 (SARS-CoV-2, CoV2). This cysteine protease, being responsible for the hydrolysis of peptide bonds between specific amino acids, plays a critical role in CoV2 replication and in assembly of new viral particles within human cells. The activity of the PL pro CoV2 is essential for the progression of coronavirus disease 2019 (COVID-19) and it constitutes a key target for the development of anti-COVID-19 drugs. Here, we identified four strong inhibitors that bind favorably to the PL pro CoV2 with the IC 50 in the nanomolar range.

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Section: Introductionmentioning

confidence: 67%

Discovery of potent inhibitors of PL^proCoV2 by screening a library of selenium-containing compounds

Węglarz-Tomczak

Tomczak

Giurg

et al. 2020

Preprint

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“…CoÀ N(1)-2.035 (15) CoÀ N(1)-2.064(1) CoÀ N(1)-2.10(1) CoÀ N(11)-2.036 (16) CoÀ N(2)-2.061 (1) CoÀ N(2)-2.067(8) CoÀ Cl(1)-2.264 (6) CoÀ Cl(1)-2.2439 (7) CoÀ Cl(1)-2.251(3) CoÀ Cl(2)-2.244 (6) CoÀ Cl (2) presence of different heteroatoms in the benzazole ring. The MIC values of the complexes 2 and 3 were low against S. aureus and B. subtilis in comparison to the cobalt complexes reported in the literature.…”

Section: 3mentioning

confidence: 99%

“…It is present in the active center of vitamin B12, which has an important role in vivo in the regulation of DNA synthesis . All vitamin B12 supplements contain cobalt, and few cobalt‐dependent proteins also exist, such as methionine aminopeptidase 2 . The pharmacological properties of known metal‐binding drugs can be modified after their coordination with cobalt .…”

Section: Introductionmentioning

confidence: 99%

“…[6] All vitamin B12 supplements contain cobalt, [6] and few cobalt-dependent proteins also exist, such as methionine aminopeptidase 2. [7] The pharmacological properties of known metal-binding drugs can be modified after their coordination with cobalt. [8] For example, cobalt releases nitrogen mustard cytotoxin in the hypoxic regions of solid tumors, which has the potential to improve drug activity and reduce toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Cobalt(II) Benzazole Derivative Complexes: Synthesis, Characterization, Antibacterial and Synergistic Activity

Nandanwar

Borkar

Wijaya³

et al. 2020

ChemistrySelect

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In this study, we synthesized the cobalt(II) chelation free complexes (1–3) with the general formula of [CoCl2L2] containing monodentate ligands (L=2‐methylbenzimidazole (L1), 2‐methylbenzoxazole (L2), and 2‐methylbenzothiazole (L3) and fully characterized by UV‐vis, FT‐IR spectroscopy, and the crystal structures of 1–3 were determined by X‐ray crystallography. Complexes 1–3 showed substantial antibacterial activity against tested bacteria. Complexes 2 and 3 were more active against S. aureus with the Minimum Inhibitory concentration (MIC) value of 12.5 μg/mL compared to other bacteria. Complexes 1–3 exhibited strong synergy with ampicillin (AMP) against Methicillin Resistant S. aureus strains (MRSA). Interestingly, complexes 2 and 3 in combination with AMP showed the membrane permeabilization of MRSA. This indicates that complexes 2 and 3 in combination with AMP had bacterial membrane disruption as a possible mechanism of action.

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“…45 Recentemente, alguns derivados de ebselen foram descritos como inibidores da atividade da enzima metionina amino peptidase 2 humana, que é essencial para o avanço de diversas doenças, incluindo tumores sólidos (Figura 8). 46…”

Section: Outras Atividades Biológicas Do Ebselen E Seus Derivadosunclassified

Ebselen: A Brief Review of its Antioxidant Capacity and Biological Applications

Nascimento¹,

Cordeiro²,

Silva³

2019

Rev. Virtual Quim.

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Ebselen is a low toxicity selenium heterocycle very studied for its antiinflammatory and antioxidant activity. In this context, ebselen is capable to mimic the glutathione peroxidase (GPx) catalytic activity, which is very important to protect cellular components from damage caused by the accumulation of reactive oxygen species (ROS). Although there are many studies on this compound, there are still divergences on its mechanism of action as GPx mimetic. In this manuscript is present a review of the last 10 years regarding the studies of ebselen mechanisms of action as antioxidant as well as some of its biological application and of its derivatives.

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Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study

Cited by 32 publications

References 45 publications

Discovery of potent inhibitors of PL^proCoV2 by screening a library of selenium-containing compounds

Discovery of potent inhibitors of PL^proCoV2 by screening a library of selenium-containing compounds

Cobalt(II) Benzazole Derivative Complexes: Synthesis, Characterization, Antibacterial and Synergistic Activity

Ebselen: A Brief Review of its Antioxidant Capacity and Biological Applications

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Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study

Cited by 32 publications

References 45 publications

Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds

Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds

Cobalt(II) Benzazole Derivative Complexes: Synthesis, Characterization, Antibacterial and Synergistic Activity

Ebselen: A Brief Review of its Antioxidant Capacity and Biological Applications

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Product

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Discovery of potent inhibitors of PL^proCoV2 by screening a library of selenium-containing compounds

Discovery of potent inhibitors of PL^proCoV2 by screening a library of selenium-containing compounds