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

Khan S., Bugday N., Rehman A. U., Ul Haq I., YAŞAR S., ÖZDEMİR İ.

APPLIED ORGANOMETALLIC CHEMISTRY, cilt.36, sa.5, 2022 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 5
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/aoc.6641
  • Dergi Adı: APPLIED ORGANOMETALLIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, BIOSIS, Chimica, Communication Abstracts, Compendex, Metadex, DIALNET, Civil Engineering Abstracts
  • Anahtar Kelimeler: 2-isobutylethiazole, molecular modeling, protein kinase, alpha-amylase, alpha-glucosidase, HETEROCYCLIC CARBENE COMPLEXES, H BOND ARYLATION, DRUG DISCOVERY, THIAZOLES, DESIGN, ANTIBACTERIAL, SOLUBILITY, CATALYSTS, TOXICITY, BEARING
  • İnönü Üniversitesi Adresli: Evet

Özet

A 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.