2. Academic Validation
  3. Halogenated Coumarin-Chalcones as Multifunctional Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors

Halogenated Coumarin-Chalcones as Multifunctional Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors

  • ACS Omega. 2021 Oct 12;6(42):28182-28193. doi: 10.1021/acsomega.1c04252.
Nisha Abdul Rehuman 1,  Jong Min Oh 2,  Lekshmi R Nath 3,  Ahmed Khames 4,  Mohamed A Abdelgawad 5,  Nicola Gambacorta 6,  Orazio Nicolotti 6,  Rakesh Kumar Jat 7,  Hoon Kim 2,  Bijo Mathew 8
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Dr. Joseph Mar Thoma Institute of Pharmaceutical Sciences & Research, Alappuzha, Kerala 690503, India.
  • 2 Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
  • 3 Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682, India.
  • 4 Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
  • 5 Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf 72341, Saudi Arabia.
  • 6 Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
  • 7 Department of Pharmaceutical Chemistry, JJTU University, Jhunjhunu 333001, India.
  • 8 Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India.
PMID: 34723016 DOI: 10.1021/acsomega.1c04252
Abstract

A series of halogenated coumarin-chalcones were synthesized, characterized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving Enzyme 1 (BACE-1) were evaluated. Compound CC2 most potently inhibited MAO-B with an IC50 value of 0.51 μM, followed by CC1 (IC50 = 0.69 μM), with a selectivity index (SI) of >78.4 and >58.0, respectively, over MAO-A. However, none of the compounds effectively inhibited MAO-A, AChE, and BChE, except for CC2 and CC3 inhibiting BChE with IC50 values of 7.00 (SI > 5.73 over AChE) and 11.8 μM, respectively. CC1 and CC2 were found to be reversible and competitive inhibitors of MAO-B, with K i values of 0.50 ± 0.06 and 0.53 ± 0.04 μM, respectively, and CC2 was also a reversible and competitive inhibitor of BChE, with a K i value of 2.84 ± 0.09 μM. The parallel artificial membrane permeability assay (PAMPA) method showed that lead candidates can cross the blood-brain barrier (BBB). The in vitro toxicity analysis on the Vero cell line (Normal African green monkey kidney epithelial cells) by MTT confirmed that both CC1 and CC2 were nontoxic up to 100 μg/mL, which is almost equivalent to 100 times of their effective concentration used in biological studies. In addition, CC1 and CC2 attenuated H2O2-induced cellular damage via their Reactive Oxygen Species (ROS) scavenging effect. These results suggest that CC1 and CC2 are selective and competitive inhibitors of MAO-B, and that CC2 is a selective and competitive inhibitor of BChE. Molecular docking studies of lead compounds provided the possible type of interactions in the targeted Enzymes. Based on the findings, both compounds, CC1 and CC2, can be considered plausible drug candidates against neurodegenerative disorders.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z