Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties
A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2′-pyrrolidine-3′,3″-piperidine]-2,4″-diones 6a‒o has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones 3a ‒ h . X-ray diffraction studies ( 6b‒d ,...
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Published in | Scientific reports Vol. 12; no. 1; p. 13880 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
16.08.2022
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | A series of 1″-(alkylsulfonyl)-dispiro[indoline-3,2′-pyrrolidine-3′,3″-piperidine]-2,4″-diones
6a‒o
has been synthesized through regioselective multi-component azomethine dipolar cycloaddition reaction of 1-(alkylsulfonyl)-3,5-bis(ylidene)-piperidin-4-ones
3a
‒
h
. X-ray diffraction studies (
6b‒d
,
h
) confirmed the structures. The majority of the synthesized analogs reveal promising antiproliferation properties against a variety of human cancer cell lines (MCF7, HCT116, A431 and PaCa2) with good selectivity index towards normal cell (RPE1). Some of the synthesized agents exhibit potent inhibitory properties against the tested cell lines with higher efficacies than the standard references (sunitinib and 5-fluorouracil). Compound
6m
is the most potent. Multi-targeted inhibitory properties against EGFR and VEGFR-2 have been observed for the synthesized agents. Flow cytometry supports the antiproliferation properties and shows the tested agents as apoptosis and necrosis forming. Vero cell viral infection model demonstrates the anti-SARS-CoV-2 properties of the synthesized agents. Compound
6f
is the most promising (about 3.3 and 4.8 times the potency of the standard references, chloroquine and hydroxychloroquine). QSAR models explain and support the observed biological properties. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-022-17883-9 |