Abstract:
Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are common in developed countries and their
incidence is increasing. The research is mostly concentrated on the exploration of novel therapies to remedy or
avert these ailments. AD and T2DM have several molecular pathways in common that contributes to their
degenerative development. A novel series of ten hybrid analogues (1–10) based on benzimidazole bearing indole
analogues were synthesized and these scaffolds were characterized by spectroscopic techniques like HR-EIMS,
13CNMR and 1
HNMR. Furthermore, the synthesized moieties were screened for α-amylase and α-glucosidase
inhibitory activities. All these synthesized analogues showed good to moderate α-amylase and α-glucosidase
inhibition potency ranging (4.90 ± 0.10 to 15.30 ± 0.60 µM) and (5.30 ± 0.10 to 16.10 ± 0.60 µM) while
acarbose was used as a reference standard (IC50 = 10 0.30 ± 0.20 µM), (IC50 = 9.80 ± 0.20 µM). Another series
of ten hybrid analogues (11–20) based on benzimidazole bearing thiazole moieties were synthesized and were
evaluated for AChE and BuChE inhibition activities. All these newly afforded analogues showed good to moderate AChE and BuChE inhibitory potential ranging of (IC50 = 0.20 ± 0.01 µM), (IC50 = 0.15 ± 0.01 µM) to (IC50
= 3.90 ± 0.20 µM), (IC50 = 3.80 ± 0.10 µM) while Donepezil was taken as a reference standard with (IC50 =
0.016 ± 0.01 µM), (IC50 = 0.30 ± 0.010 µM).The scaffolds were also characterized using spectroscopic techniques such as HR-EIMS, 13CNMR and 1
HNMR for a better understanding of their structure. SAR was done for all
synthesized analogues for substituents.In addition, docking research was conducted to determine the binding
mode of interaction between the active site of analogues and targeted enzymes. This work aims to estimate the
potential of the synthesized scaffolds as competitors to existing drugs. Incorporating molecular docking analysis
with in vitro activities improves the accuracy of predictions and validates the possibility of these compounds as
options for treating type-2 diabetes and Alzheimer’s disease.
