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Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors
- Source :
- ACS Medicinal Chemistry Letters
- Publication Year :
- 2021
-
Abstract
- For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were proposed as potential inhibitors of the SARS-CoV-2 main viral protease (3-chymotrypsin-like, 3CLpro). Based on the created pharmacophore model of the active site of the protease, a group of compounds were modeled and tested for activity against 3CLpro. The 3CLpro activity was measured using the fluorogenic substrate Dabcyl-VNSTLQSGLRK(FAM)MA;the efficiency of the proposed approach was confirmed by comparison with literature data for ebselen and disulfiram. The results of the experiments performed with bispidine compounds showed that 14 compounds exhibited activity in the concentration range 1-10 μM, and 3 samples exhibited submicromolar activity. The structure-activity relationship studies showed that the molecules containing a carbonyl group in the ninth position of the bicycle exhibited the maximum activity. Based on the experimental and theoretical results obtained, further directions for the development of this topic were proposed. ©
- Subjects :
- Protease
biology
Ebselen
Stereochemistry
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
medicine.medical_treatment
Organic Chemistry
bispidinone
Active site
molecular docking
Note
Biochemistry
Carbonyl group
inhibition
3,7-diazabicyclo[3.3.1]nonane
chemistry.chemical_compound
chemistry
Viral protease
Drug Discovery
biology.protein
medicine
Nonane
Pharmacophore
SARS-CoV-2 main viral protease
Subjects
Details
- ISSN :
- 19485875
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- ACS medicinal chemistry letters
- Accession number :
- edsair.doi.dedup.....11d168674578bd817d95c51996602ffc