Design, synthesis and cytotoxic activity of spiro(oxindole-3-3'-pyrrolidine) derivatives

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dc.authoridAhmet Cenk Andaç / 0000-0002-4545-3500en_US
dc.authorscopusidAhmet Cenk Andaç / 20336962400
dc.authorwosidAhmet Cenk Andaç / AAW-5539-2020
dc.contributor.authorKonyar, Dilan
dc.contributor.authorAndaç, Ahmet Cenk
dc.contributor.authorBüyükbingol, Erdem
dc.date.accessioned2020-08-30T20:07:55Zen_US
dc.date.available2020-08-30T20:07:55Zen_US
dc.date.issued2018
dc.departmentİstinye Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümüen_US
dc.description.abstractBackground: Spiro[pyrrolidine-3,3'-oxindole] compounds are reported to be highly bioactive natural and synthetic products. Initially, spirooxindole alkaloids were isolated from plants of the Apocynaceae and Rubiaceae families, which were found to have a common scaffold, spiro[pyrrolidine-3,3'-oxindole], exhibiting anticancer activities., we specifically aimed at the synthesis, characterization and anticancer activity of novel spiro[pyrrolidine-3,3'-oxindole] derivatives, compounds 6a-c and 7. Methods: The synthesis was initiated by Knovenegal condensation of indole-2-one with an appropriate benzaldehyde in presence of piperidine to afford compounds 3a-c. Compounds 6a-c were synthesized by an asymmetric 1,3-dipolar cycloaddition between compounds 3a-c and (2S, 3R)-2, 3, 5, 6-tetrahydro-2, 3-diphenyl-1, 4-oxazin-6-one, which is an intermediate compound formed by the Schiff base reaction between 3-methyl-butanal and (2S, 3R)-2, 3, 5, 6-tetrahydro-2, 3-diphenyl-1,4- oxazin-6-one, in presence of molecular sieves (4A) under argon atmosphere. Compound 6a was then reacted with ethylamine-HCl in THF at room temperature to yield compound 7. Results: Cytotoxic effects of the compounds synthesized were determined on Huh7, MV, HCT116 and MCF7 cancer cell lines by the NCI-60 Sulforhodamine B Assay, using (S)-(+)-Camptothecin as a positive control. In general, target compounds showed better cytotoxic activities against the MCF7 and HCT116 cancer cell lines. It was found that compound 7 exhibited the most potent inhibitory activity with IC50 values of 4.8 mu M, 3.9 mu M, 14.9 mu M and 8.2 mu M against the MCF7, HCT116, MV and Huh7 cell lines, respectively. Conclusion: It was determined that compounds 6a&6b possess C6'(S)|C8'(R)|C9'(R) stereochemistry and compound 7 adopts C2'(S)|C4'(R)|C5'(R) stereochemistry. Cytotoxicity studies suggest that compound 7 gave rise to the highest anticancer activity against MCF7, HCT116, and Huh7 cancer cell lines.en_US
dc.description.sponsorshipResearch Fund of Ankara UniversityAnkara University [10B3336001]en_US
dc.description.sponsorshipThis study is funded by the Research Fund of Ankara University (Grant No. 10B3336001). The authors acknowledge Dr. Rengul Atalay at the Cancer System Biology Laboratory, Graduate School of Informatics, Middle East Technical University-Ankara, Turkey, and Deniz Cansen Yildirim at the Department of Molecular Biology and Genetics (DMBG), Faculty of Science, Bilkent University (BU) at Ankara, Turkey, for implementing the cytotoxic activity studies at the DMBG laboratories at BU-Ankara, Turkey. We also would like to thank the Instrumental Analysis Facility in the School of Farmacy at Ankara University-Ankara, Turkey for allowing us to use the NMR, LC-MS and Elemental Analysis instruments therein.en_US
dc.identifier.citationKonyar, D., Andac, C. A., & Buyukbingol, E. (2018). Design, Synthesis and Cytotoxic Activity of Spiro (oxindole-3-3'-pyrrolidine) Derivatives. Letters in Drug Design & Discovery, 15(1), 37-45.en_US
dc.identifier.doi10.2174/1570180814666170810120634en_US
dc.identifier.endpage45en_US
dc.identifier.issn1570-1808en_US
dc.identifier.issn1875-628Xen_US
dc.identifier.issue1en_US
dc.identifier.scopus2-s2.0-85041688089en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage37en_US
dc.identifier.urihttps://doi.org/10.2174/1570180814666170810120634en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12713/854en_US
dc.identifier.volume15en_US
dc.identifier.wosWOS:000423790800006en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.institutionauthorAndaç, Ahmet Cenken_US
dc.language.isoenen_US
dc.publisherBentham Science Publ Ltden_US
dc.relation.ispartofLetters In Drug Design & Discoveryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectOxindoleen_US
dc.subjectSpiro Pyrrolidino Oxindoleen_US
dc.subject1,3-Dipolar Cycloaddition Reactionen_US
dc.subjectCytotoxic Activityen_US
dc.subjectCanceren_US
dc.subjectDrug Designen_US
dc.titleDesign, synthesis and cytotoxic activity of spiro(oxindole-3-3'-pyrrolidine) derivativesen_US
dc.typeArticleen_US

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