Structure based design, synthesis of novel fused triazole-thiazole derivatives and their comparative study on Alzheimer disease along with in silico modeling

Abstract

In this approach, fused triazole thiazole derivatives (1–14) were synthesized and designed as dual inhibitors of AChE and BuChE which exhibit promising inhibitory activity to cure one of the progressive disorders, Alzheimer’s disease. Different spectroscopic techniques (13C NMR, 1H NMR and HREI-MS) were employed for the synthetic confirmations of all the derivatives. Using the standard drug donepezil (IC50 = 10.60 ± 0.20 for AChE and 11.80 ± 0.49 µM for BuChE). All the analogues in the current series showed a wide range of inhibitory potentials such as (IC50 = 7.20 ± 0.10 to 17.50 ± 0.10 µM for AChE and IC50 = 8.10 ± 0.20 to 18.20 ± 0.10 µM for BuChE). The nature, number and position of the attached substituents in the phenyl ring greatly influenced the inhibitory activity of the current analogues in the series. However, Analogue 4 with IC50 values (7.20 ± 0.10, 8.10 ± 0.20 µM) showed immense potency due to para substituted tri-fluoro methyl moiety. Molecular docking studies and ADME analysis was also conducted for the excellent binding interactions with target enzymes and drug like properties of the potent analogues.

Keywords

• Fused triazole-thiazole
• Alzheimer’s disease
• Synthesis
• Molecular docking & drug likeness-ADME