Design and development of molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles as potential multifunctional agents to treat Alzheimer's disease

Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

“…For instance, Lee et al analyzed several phlorotannins that interacted also with some of the residues above referred, especially eckol (Figure 7) [53]. Kashyap et al observed that two plant natural compounds, reserpine and ajmalicine (Figure 7), also interacted with some of the most rele- Similar to what occurs for synthetic compounds, flavone derivatives (PDB#6EQM), specifically baicalein and diosmetin derivatives [57], 2-phenylbenzimidazoles (PDB#1FKN) [58], 7,8-dihydroxyflavone derivatives (PDB#2ZHS) [59], molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles (PDB#2ZJM), especially compound 4 [60], and quinazolinonebased hydrazones (PDB#4B70) [61], also have demonstrated very promising in silico results that can result in novel drug candidates for BACE-1 inhibition, as shown in (Figure 8). Tran et al [62] built a 2D-QSAR model (R 2 of 0.83) based on the structure of BACE-1 inhibitors found in the literature to identify novel potential inhibitors in a library of chalcone derivatives.…”

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

“…The enzyme kinetics study of 63 against AChE indicated a mixed type of inhibition ( K i = 0.030 µM). Compound 63 may be deemed as a notable lead with multifunctional actions against AD 189 ( Table 3 ).…”

Design and Development of Multifunctional Hybrids of Ferulic Acid and 1,3,4-Oxadiazoles for the Treatment of Alzheimer’s Disease

“…The researchers are now firmly convinced that the targeting of a single node of the Alzheimer's classical pathway by conventional therapeutics only exerts a little effect on the multifactorial AD network. These findings suggest an immense requirement of novel drugs with a strong potential of treatment that modulates multiple targets that decelerate the AD progression rather than a diminution of symptoms (18)(19)(20).…”