Synthesis, Characterization and Biological Evaluation of Ester Derivatives of 4-(Diethylamino)salicylaldehyde as Cholinesterase, and Tyrosinase Inhibitors

Abstract

Alzheimer's disease, one of the diseases that still has no a specific therapy, has become a major public health issue owing to the increasing population of the elderly, particularly in rich countries. Inhibitory of cholinesterase enzymes (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which hydrolyze acetylcholine (ACh) and butyrylcholine (BCh) neurotransmitters, have recently become a choice for the therapy of this disease. Therefore, there is currently a great demand for novel enzyme inhibitors with desirable properties for applying in the treatment of AD. In this study, a series of ester derivatives of 4-(diethylamino)salicylaldehyde (1-5) were successfully prepared and structurally illuminated with FT-IR, 1 H-and 13 C NMR spectroscopy. The inhibitory properties of the synthesized molecules on AChE, BChE, and tyrosinase enzymes were investigated, respectively. Compound 1 indicated potent inhibitory activity against BChE with 87.28±0.87% inhibition better than galanthamine (73.83±0.25 %inhibition) employed as standard. Compound 3 showed significant inhibitory effect against tyrosinase with 87.73±0.22 % inhibition, which is better than kojic acid utilized as standard. The obtained results clearly revealed that some of these molecules have the potential to be used as potent enzyme inhibitor candidates in the future studies.

Some Novel Schiff Base Derivatives as Promising Cholinesterase Inhibitors With Antioxidant Activity Against Alzheimer’s Disease: Synthesis, Characterization and Biological Evaluation

“…In this research, the inhibitory performance of new compounds towards cholinesterases was determined, respectively [32]. The method used in the present study was explained in detail in our previous studies [27,29,31,33].…”

Anticholinesterase and antioxidant activities of novel heterocyclic Schiff base derivatives containing an aryl sulfonate moiety

“…In the recent years, the incidence of AD is increasing, especially in people over 60 years of age, and it is seen that this disease has become a cause of serious morbidity. [3][4][5][6] Studies have been carried out for many years to reveal the causes of the disease; and as a result of these studies, it is stated that the most important pathological lesions suggested in the formation of AD are amyloid plaques and neurofibrillary tangles. [7,8] On the other hand, various hypotheses have been put forward in the formation of AD, the most important of which is the cholinergic hypothesis.…”

“…In the recent years, the incidence of AD is increasing, especially in people over 60 years of age, and it is seen that this disease has become a cause of serious morbidity. [ 3–6 ]…”

Design, Docking, Synthesis and Biological Evaluation of Novel Nicotinohydrazone Derivatives as Potential Butyrylcholinesterase Enzyme Inhibitor

“…However, it is reported that these inhibitors have serious side effects in clinical application [11,14] . Therefore, there is a great need for the development of new cholinesterase inhibitors [15a–e] …”

“…It is reported in many studies that these compounds have various biological activities in a wide broad spectrum including antioxidant [28b,29a–c] , anticonvulsant [30] , antidepressant [31] , antimicrobial [32] and antitumoral [33] and so forth. On the other hand, it is well known that hydrazone derivatives also act as AChE, BChE and tyrosinase inhibitors [15d,28e, 29b, 34] . Apart from that, they indicate various biological activities such as analgesic and anti‐inflammatory [35a–b] …”