Synthesis, Docking Study and Biological Activities Evaluation of 1‐Amidoalkyl‐2‐naphthol Derivatives as Dual Inhibitors of Cholinesterase and α‐Glucosidase

Abstract

An efficient green synthesis of 1-amidoalkyl-2-naphthol derivatives 4 a-s has been developed, employing phenylboronic acid, by a three component one-pot condensation reaction of 2naphthol, a wide range of functionalized aromatic aldehydes and acetamide, or acrylamide under solvent-free conditions. This new protocol has the rewards of ecologically benign, easy workup along with good to excellent yields. Moreover, selected compounds were screened towards inhibition of cholinesterase. In vitro studies showed that some synthesized compounds have significant both AChE and BChE inhibitory activities compared to Galanthamine (reference drug). Compounds 4 p and 4 s were the most effective showing high potential AChE and BChE inhibitory activities with respective IC 50 values of 13.81 � 0.54 μM and 31.70 � 1.29 μM. Subsequent evaluation of the α-glucosidase inhibitory activity of the target molecules revealed that compound 4 s with an IC 50 value of 2.05 � 0.05 μM exhibited highest activity. These preliminary results provide promising sources of multifunctional agents and sheds light on their potential usage in medicine and in the pharmaceutical industries. Using molecular docking approach, we tried to get insights into binding interactions of our synthesized compounds to act as AChE and BChE inhibitors and understand the facts that underlie the relationships between structural modifications on these ligands and their efficacy.

Amidoalkyl Naphthols as Important Bioactive Substances and Building Blocks: A Review on the Current Catalytic Mannich-Type Synthetic Approaches

“…The 1-amidoalkyl-2-naphthols possess diverse biological properties, such as antiviral, antibacterial, antifungal, and antiparasitic qualities [18][19][20][21][22]. Furthermore, members of this family are promising antioxidants, which also show cholinesterase and α-glucosidase inhibitory activities [23][24][25].…”

“…As a result of an in vitro screening against Leishmania donovani, followed by a molecular docking study and an in silico study of the ADME (absorption, distribution, metabolism, and excretion) properties of the molecules, four of them (compounds 19-22, Figure 6) were distinguished as the most promising anti-leishmanial agents possessing good drug-like characteristics. Boudebbous et al, synthesized 19 amidoalkyl naphthols and evaluated their cholinesterase and α-glucosidase inhibitory activities [23]. The results of the in vitro assays were backed by a docking study of selected derivatives.…”

Greener organic synthetic methods: Sonochemistry and heterogeneous catalysis promoted multicomponent reactions

“…MCR methodologies mediated by ultrasonic irradiation and nanocatalysis were developed for the preparation of 1-amidoalkyl-2-naphthol derivatives ( 4 8 ), an important class of compounds that showed inhibition of acetyl- and butyrylcholinesterases (AChE and BChE, respectively) that are target to the treatment of neurodegenerative diseases [242] . These synthetic approaches are based on one-pot condensation between β -naphthol ( 69 ), aldehydes ( 1 ), and amides ( 1 4 7 ), under solvent-free conditions ( Scheme 55 ).…”

Sonochemical‐Promoted Multicomponent Synthesis of a New Amidoalkyl Naphthol Derivative Catalyzed by [(Msim)Cl] Ionic Liquid and Assessment of Its Nonlinear Optical Properties

“…[14] Among these compounds, amidoalkyl naphthol derivatives, which are of interest and specific value because of their sub-structures are found in various bioactive compounds such as potent drugs and natural products. [15] Furthermore, amidoalkyl naphthol molecules are effective intermediates as they can be easily transformed into 1,3-oxazine-containing derivatives via Vilsmeier cyclization. [16] 1,3-Oxazine derivatives have shown ubiquitous properties that can be of great benefit in biochemical and physiochemical applications.…”

“…On the other hand, compounds with a 1,3‐amino oxygenated motif are found to possess a broad range of biological activities [14] . Among these compounds, amidoalkyl naphthol derivatives, which are of interest and specific value because of their sub‐structures are found in various bioactive compounds such as potent drugs and natural products [15] . Furthermore, amidoalkyl naphthol molecules are effective intermediates as they can be easily transformed into 1,3‐oxazine‐containing derivatives via Vilsmeier cyclization [16] .…”