Spiroindole-containing compounds bearing phosphonate group of potential Mpro-SARS-CoV-2 inhibitory properties.
Eur J Med Chem
; 258: 115563, 2023 Jun 10.
Article
in English
| MEDLINE | ID: covidwho-20233088
ABSTRACT
Microwave-assisted reaction of 3,5-bis((E)-ylidene)-1-phosphonate-4-piperidones 3aâg with azomethine ylide (produced through interaction of isatins 4 and sarcosine 5) cycloaddition afforded the corresponding (dispiro[indoline-3,2'-pyrrolidine-3',3â³-piperidin]-1â³-yl)phosphonates 6aâl in excellent yields (80-95%). Structure of the synthesized agents was evidenced by single crystal X-ray studies of 6d, 6i and 6l. Some of the synthesized agents revealed promising anti-SARS-CoV-2 properties in the viral infected Vero-E6 cell technique with noticeable selectivity indices. Compounds 6g and 6b are the most promising agents synthesized (R = 4-BrC6H4, Ph; R' = H, Cl, respectively) with considerable selectivity index values. Mpro-SARS-CoV-2 inhibitory properties supported the anti-SARS-CoV-2 observations of the potent analogs synthesized. Molecular docking studies (PDB ID 7C8U) are consistent with the Mpro inhibitory properties. The presumed mode of action was supported by both experimentally investigated Mpro-SARS-CoV-2 inhibitory properties and explained by docking observations.
Full text:
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Collection:
International databases
Database:
MEDLINE
Type of study:
Observational study
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Prognostic study
Language:
English
Journal:
Eur J Med Chem
Year:
2023
Document Type:
Article
Affiliation country:
J.ejmech.2023.115563
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