Benzofuran Hybrids as Cholinesterase (AChE and BChE) Inhibitors: In Vitro, In Silico, and Kinetic Studies

• Published in: Russian journal of bioorganic chemistry Vol. 48; no. 6; pp. 1322 - 1337
• Main Authors: Ali, I., Rafique, R., Khan, K. M., Chigurupati, S., Ji, X., Wadood, A., Rehman, A. U., Salar, U., Alyamani, N. M., Hameed, S., Taha, M., Hussain, S., Perveen, S.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.12.2022; Springer Nature B.V
• Subjects: Alzheimer's disease; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cholinergics; Cholinesterase; Enzymes; Inhibitors; Life Sciences; Organic Chemistry; AChE; BChE; butyrylcholinesterase; benzofuran; molecular modelling; acetylcholinesterase; kinetics
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162022060061

Cholinesterase enzymes (AChE and BChE) play a vital function in cholinergic deficit that precedes to Alzheimer’s disease (AD). The inhibition of these enzymes with small compounds has been observed as an attractive method for the treatment of AD. The present study reveals the inhibitory activities of benzofuran-hybrid analogs against both the AChE and BChE enzymes. All molecules exhibited varying degree of cholinesterase inhibitory potentials with IC 50 value ranges for AChE (IC 50 = (21.04 ± 0.51)–(87.17 ± 0.15) μM) and BChE (IC 50 = (22.2 ± 0.15)–(90.17 ± 0.10) μM) on comparison with standard donepezil (AChE; IC 50  = 19.08 ± 0.05 μM and BChE; IC 50 = 19.58 ± 0.03 μM). Five compounds ( IV ) (AChE; IC 50 = 21.04 ± 0.51 μM and BChE; IC 50 = 22.2 ± 0.15 μM), ( VI ) (AChE; IC 50 = 35.86 ± 0.23 μM and BChE; IC 50 = 36.16 ± 0.33 μM), ( VIII ) (AChE; IC 50 = 24.86 ± 0.23 μM and BChE; IC 50 = 25.16 ± 0.13 μM), ( XV ) (AChE; IC 50 = 31.04 ± 0.52 μM and BChE; IC 50 = 33.04 ± 0.22 μM), ( XVI ) (AChE; IC 50 = 31.86 ± 0.23 μM and BChE; IC 50  = 32.16 ± 0.33 μM), and ( XX ) (AChE; IC 50 = 41.33 ± 0.02 μM and BChE; IC 50 = 42.33 ± 0.12 μM) exhibited excellent to moderate inhibitory potential and may serve as dual inhibitors against both enzymes. The molecular modelling study was performed to analyze their binding interaction with AChE and BChE proteins. The kinetic study showed that all derivatives were found to be non-competitive type inhibitors. This study helpful for identification of potential leads as anticholinesterase inhibitors for the treatment of AD.