Spiroindole-containing compounds bearing phosphonate group of potential Mpro-SARS-CoV-2 inhibitory properties

Bekheit, Mohamed S., Panda, Siva S., Kariuki, Benson M. ORCID: https://orcid.org/0000-0002-8658-3897, Mahmoud, Sara H., Mostafa, Ahmed and Girgis, Adel S. 2023. Spiroindole-containing compounds bearing phosphonate group of potential Mpro-SARS-CoV-2 inhibitory properties. European Journal of Medicinal Chemistry 258 , 115563. 10.1016/j.ejmech.2023.115563

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Abstract

Microwave-assisted reaction of 3,5-bis((E)-ylidene)-1-phosphonate-4-piperidones 3a‒g with azomethine ylide (produced through interaction of isatins 4 and sarcosine 5) cycloaddition afforded the corresponding (dispiro[indoline-3,2′-pyrrolidine-3′,3″-piperidin]-1″-yl)phosphonates 6a‒l 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Publisher:	Elsevier
ISSN:	0223-5234
Date of First Compliant Deposit:	4 September 2023
Date of Acceptance:	9 June 2023
Last Modified:	10 Nov 2024 01:45
URI:	https://orca.cardiff.ac.uk/id/eprint/162228

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