Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors.
Bioorg Med Chem Lett
; 23(24): 6549-54, 2013 Dec 15.
Article
in En
| MEDLINE
| ID: mdl-24268549
ABSTRACT
A series of methionine-proline dipeptide derivatives and their analogues were designed, synthesized and assayed against the serotype 2 dengue virus NS2B-NS3 protease, and methionine-proline anilides 1 and 2 were found to be the most active DENV 2 NS2B-NS3 competitive inhibitors with Ki values of 4.9 and 10.5 µM. The structure and activity relationship and the molecular docking revealed that L-proline, L-methionine and p-nitroaniline in 1 and 2 are the important characters in blocking the active site of NS2B-NS3 protease. Our current results suggest that the title dipeptidic scaffold represents a promising structural core to discover a new class of active NS2B-NS3 competitive inhibitors.
Key words
4-(N,N'-dimethyl)-aminopyridine; 4-Nitroaniline; DCC; DCM; DENV; DMAP; Dengue virus NS2B-NS3 protease; EtOAc; EtOH; HQRJJHXKCFABSI-UONOGXRCSA-N; K(i); Methionine; Methionineproline anilides; NS2B-NS3; Proline; SAR; TFA; dengue virus; dichloromethylene; dicyclohexylcarbodiimide; ethyl acetate; ethyl alcohol; inhibition constant; nonstructural protein 2B and 3; structure and activity relationship; trifluoroacetic acid
Full text:
1
Database:
MEDLINE
Main subject:
Protease Inhibitors
/
Serine Endopeptidases
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Viral Nonstructural Proteins
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Dengue Virus
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Anilides
Language:
En
Journal:
Bioorg Med Chem Lett
Year:
2013
Type:
Article