Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties.

Autor: Fawazy NG; Department of Pesticide Chemistry, National Research Centre, Dokki, Giza, 12622, Egypt., Panda SS; Department of Chemistry and Physics, Augusta University, Augusta, GA, 30912, USA., Mostafa A; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, 12622, Egypt., Kariuki BM; School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK., Bekheit MS; Department of Pesticide Chemistry, National Research Centre, Dokki, Giza, 12622, Egypt., Moatasim Y; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, 12622, Egypt., Kutkat O; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, 12622, Egypt., Fayad W; Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622, Egypt., El-Manawaty MA; Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622, Egypt., Soliman AAF; Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622, Egypt., El-Shiekh RA; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., Srour AM; Department of Therapeutic Chemistry, National Research Centre, Dokki, Giza, 12622, Egypt., Barghash RF; Department of Pesticide Chemistry, National Research Centre, Dokki, Giza, 12622, Egypt., Girgis AS; Department of Pesticide Chemistry, National Research Centre, Dokki, Giza, 12622, Egypt. girgisas10@yahoo.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Aug 16; Vol. 12 (1), pp. 13880. Date of Electronic Publication: 2022 Aug 16.
DOI: 10.1038/s41598-022-17883-9
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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