Synthesis of amantadine clubbed N-aryl amino thiazoles as potent urease, alpha-amylase & alpha-glucosidase inhibitors, kinetic and molecular docking studies

A series of ten novel compounds were synthesized by incorporating a 1,3 thiazole core into amantadine and their structures were validated using different analytical and spectral methods such as FTIR, EI-MS, H-1 NMR, and C-13 NMR. The antibacterial and enzyme inhibitory properties of these newly synthesized compounds were evaluated. Remarkably, the compounds exhibited significant antibacterial activity against Escherichia coli and Bacillus subtilis. Additionally, the in vitro inhibitory activities of the synthesized compounds, against alpha-amylase, alpha-glucosidase, and urease were investigated. Among the tested compounds, compound 6d demonstrated potent and selective inhibition of alpha-amylase IC50 = 97.37 +/- 1.52 mM, while acarbose was used as positive control and exhibited IC50 = 5.17 +/- 0.25 mu M. Compound 6d and 6e exhibited prominent inhibition against alpha-glucosidase IC50 = 38.73 +/- 0.80 mu M and 41.63 +/- 0.26 mu M respectively. Furthermore, compound 6d inhibited urease with exceptional efficacy IC50 = 32.76 mu M, while positive control thiourea showed more prominent activity having IC50 = 1.334 mu M. Molecular docking studies disclosed the binding mechanism and affinity of these new inhibitors within the binding sites of various amino acids. To investigate the association between molecular structural characteristics and inhibitory actions of synthesized derivatives, preliminary structure-activity relationship (SAR) studies were performed. These findings indicated that compounds 6a, 6c, 6d and 6e are potential candidates for hit-to-lead follow-up in the drug-discovery process for treating diabetes and hyperglycemia.

Automated summary

A series of novel compounds containing a 1,3 thiazole core were synthesized and their structures were confirmed using various analytical and spectral methods. These compounds exhibited significant antibacterial activity against Escherichia coli and Bacillus subtilis, as well as inhibitory activities against alpha-amylase, alpha-glucosidase, and urease. Compound 6d showed potent and selective inhibition of alpha-amylase, while compounds 6d and 6e exhibited prominent inhibition against alpha-glucosidase. Molecular docking studies revealed the binding mechanism and affinity of these new inhibitors within the binding sites of various amino acids.