Synthesis, molecular docking, and biological evaluation of 5-alkyl(aryl)-2-isobutylthiazole derivatives: As ?-amylase, ?-glucosidase, and protein kinase inhibitors

Basit Öğe Kaydı
dc.authoridKhan, Siraj/0000-0003-1948-452X
dc.authorwosidRehman, Asim Ur/J-4207-2015
dc.contributor.authorKhan, Siraj
dc.contributor.authorBugday, Nesrin
dc.contributor.authorRehman, Asim Ur
dc.contributor.authorUl Haq, Ihsan
dc.contributor.authorYasar, Sedat
dc.contributor.authorOzdemir, Ismail
dc.date.accessioned2024-08-04T20:51:45Z
dc.date.available2024-08-04T20:51:45Z
dc.date.issued2022
dc.departmentİnönü Üniversitesien_US
dc.description.abstractA series of 18 biologically active C5-arylated-2-isobutylthiazole derivatives that were synthesized by Pd-NHC complexes [Pd(mu-Cl)Cl (NHC)](2), NHC = SIXyl, 2), (LCl2Pd-NHC, L = PPh3, 3), (LCl2Pd-NHC, L = Py, 4), (LCl2Pd-NHC, L = 3-CHO-Py, 5) catalyzed C-H bond activation reactions. The catalytic activity of Pd-NHC complexes was examined on the C-H bond activation reaction of 2-isobutylthiazole. All Pd-NHC complexes were characterized by( 1)H nuclear magnetic resonance specroscopy (NMR), C-13 NMR, fouirer transform infrared spektroscopy (FTIR), quadrupole-time of flying-liquit cromotagraphy/mass spektroscopy (Q-TOF-LC/MS), gas chromatography-mass spectrometry (GCMS), and melting point detection technique. The physicochemical properties, pharmacokinetics, and drug-likeness were calculated by SwissADME. PkCSM database was used to calculate toxicities profile. All the products (6a-6s) were additionally assessed in vitro for their antidiabetic potential using alpha-amylase and alpha-glucosidase inhibitory activities. The protein kinase activity was performed to evaluate their anticancer activities. All the compounds possess drug-like characters as they followed Lipinski's rule of five (RO5). Almost all the compounds showed no to fewer toxicities. In addition, other than the compounds, that is, 6a, 6b, 6c, 6m, 6n, 6p, and 6s, the rest of the compounds showed good alpha-glucosidase inhibitory potential (IC50 7.17 +/- 0.201 to 74.08 +/- 0.244 mu g/ml) when compared with acarbose standard (IC50 16.59 +/- 0.135 mu g/ml). All compounds had moderate to good inhibitory potential against the alpha-amylase enzyme, with IC50 values ranging from 12.00 +/- 0.289 to 76.15 +/- 0.477 mu g/ml. Eleven analogs (6e, 6f, 6g, 6h, 6j, 6k, 6l, 6n, 6o, 6p, and 6r) showed good to moderate activity. Seven analogs (6a, 6b, 6c, 6d, 6i, 6m, and 6s) showed no alpha-amylase inhibitory activity. The protein kinase inhibition potential was determined for the first time, and the compounds 6d, 6e, 6f, 6h, 6k, 6p, and 6r depicted activity with the zone of inhibition in the range of 9 +/- 1.3 to 19 +/- 1.5 mm. The ligands and active site binding interactions of alpha-glucosidase, alpha-amylase, and protein kinase enzymes were also studied using molecular modeling.en_US
dc.description.sponsorshipHigher Education Commission (HEC) of Pakistan [518-78015-2MD5-047 [50043709]]en_US
dc.description.sponsorshipSiraj Khan was financially supported by the Indigenous Ph.D. fellowship (PIN NO. 518-78015-2MD5-047 [50043709]) granted by the Higher Education Commission (HEC) of Pakistan. We would like to thank the Higher Education Commission of Pakistan.en_US
dc.identifier.doi10.1002/aoc.6641
dc.identifier.issn0268-2605
dc.identifier.issn1099-0739
dc.identifier.issue5en_US
dc.identifier.scopus2-s2.0-85125784149en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1002/aoc.6641
dc.identifier.urihttps://hdl.handle.net/11616/100513
dc.identifier.volume36en_US
dc.identifier.wosWOS:000765625800001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofApplied Organometallic Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subject2-isobutylethiazoleen_US
dc.subjectmolecular modelingen_US
dc.subjectprotein kinaseen_US
dc.subjectalpha-amylaseen_US
dc.subjectalpha-glucosidaseen_US
dc.titleSynthesis, molecular docking, and biological evaluation of 5-alkyl(aryl)-2-isobutylthiazole derivatives: As ?-amylase, ?-glucosidase, and protein kinase inhibitorsen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu