Synthesis of Thiazole-Chalcone Hybrid Molecules: Antioxidant, Alpha(a)-Amylase Inhibition and Docking Studies

The molecular hybrid approach is very significant to combat various drug-resistant disorders. A simple, convenient, and cost-effective synthesis of thiazole-based chalcones is accomplished, using a molecular hybrid approach, in two steps. The compound 1-(2-phenylthiazol-4-yl)ethanone (3) was used as the main intermediate for the synthesis of 3-(arylidene)-1-(2-phenylthiazol-4-yl)prop-2-en-1-ones (4a-f). Thin layer chromatography was used to testify the formation and purity of all synthesized compounds. Further structural confirmation of all compounds was achieved via different spectroscopic techniques (UV, FT-IR, H-1- and C-13-NMR) and elemental analysis. All synthesized compounds were tested for their a-amylase inhibition and antioxidant potential. The cytotoxic property of compounds was also tested with in vitro haemolytic assay. All tested compounds showed moderate to excellent a-amylase inhibition and antioxidant activity. All tested compounds are found safe to use due to their less toxicity when compared to the standard Triton X. The molecular docking simulation study of all synthesized compounds was also conducted to examine the best binding interactions with human pancreatic a-amylase (pdb: 4 W93) using AutodockVina. The molecular docking results authenticated the in vitro amylase inhibition results, i.e., 3-(3-Methoxyphenyl)-1-(2-phenylthiazol-4-yl)prop-2-en-1-one (4e) exhibited lowest IC50 value 54.09 +/- 0.11 mu M with a binding energy of -7.898 kcal/mol.

Automated summary

The molecular hybrid approach is used to synthesize thiazole-based chalcones in a simple and cost-effective manner. The synthesized compounds show promising a-amylase inhibition and antioxidant activity. They are also found to be safe for use compared to the standard Triton X. Molecular docking simulations confirm the in vitro amylase inhibition results and identify a compound with the lowest IC50 value.