PMID- 32606589
OWN - NLM
STAT- MEDLINE
DCOM- 20210330
LR  - 20240328
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 14
DP  - 2020
TI  - Comparative Cholinesterase, alpha-Glucosidase Inhibitory, Antioxidant, Molecular 
      Docking, and Kinetic Studies on Potent Succinimide Derivatives.
PG  - 2165-2178
LID - 10.2147/DDDT.S237420 [doi]
AB  - INTRODUCTION: The current study was designed to synthesize derivatives of 
      succinimide and compare their biological potency in anticholinesterase, 
      alpha-glucosidase inhibition, and antioxidant assays. METHODS: In this research, 
      two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) 
      cyclohexanecarbaldehyde (Compound 1) and 
      (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were 
      synthesized using Michael addition. Both the compounds, ie, 1 and 2 were 
      evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase 
      (BChE), antioxidant, and alpha-glucosidase inhibitory potentials. Furthermore, 
      molecular docking was performed using Molecular Operating Environment (MOE) to 
      explore the binding mode of both the compounds against different enzymes. 
      Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of 
      initial enzyme velocity versus the reciprocal of substrate concentration in the 
      presence of synthesized compounds and standard drugs were constructed using 
      Michaelis-Menten kinetics. RESULTS: In AChE inhibitory assay, compounds 1 and 2 
      exhibited IC(50) of 343.45 and 422.98 microM, respectively, against AChE enzyme. 
      Similarly, both the compounds showed IC(50) of 276.86 and 357.91 microM, 
      respectively, against BChE enzyme. Compounds 1 and 2 displayed IC(50) of 157.71 
      and 471.79 microM against alpha-glucosidase enzyme, respectively. In a similar pattern, 
      compound 1 exhibited to be more potent as compared to compound 2 in all the three 
      antioxidant assays. Compound 1 exhibited IC(50) values of 297.98, 332.94, and 
      825.92 microM against DPPH, ABTS, and H(2)O(2) free radicals, respectively. Molecular 
      docking showed a triple fold in the AChE and BChE activity for compound 1 
      compared with compound 2. The compound 1 revealed good interaction against both 
      the AChE and BChE enzymes which revealed the high potency of this compound 
      compared to compound 2. CONCLUSION: Both succinimide derivatives exhibited 
      considerable inhibitory activities against cholinesterases and alpha-glucosidase 
      enzymes. Of these two, compound 1 revealed to be more potent against all the 
      in-vitro targets which was supported by molecular docking with the lowest binding 
      energies. Moreover, compound 1 also proved to have antiradical properties.
CI  - (c) 2020 Ahmad et al.
FAU - Ahmad, Ashfaq
AU  - Ahmad A
AD  - Department of Pharmacy, Sarhad University of Science & Technology, Peshawar, KPK, 
      Pakistan.
AD  - Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, 
      Chakdara, 18000, KP, Pakistan.
FAU - Ullah, Farhat
AU  - Ullah F
AD  - Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, 
      Chakdara, 18000, KP, Pakistan.
FAU - Sadiq, Abdul
AU  - Sadiq A
AD  - Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, 
      Chakdara, 18000, KP, Pakistan.
FAU - Ayaz, Muhammad
AU  - Ayaz M
AUID- ORCID: 0000-0002-4299-2445
AD  - Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, 
      Chakdara, 18000, KP, Pakistan.
FAU - Saeed Jan, Muhammad
AU  - Saeed Jan M
AUID- ORCID: 0000-0003-2411-6510
AD  - Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, 
      Chakdara, 18000, KP, Pakistan.
FAU - Shahid, Muhammad
AU  - Shahid M
AUID- ORCID: 0000-0002-6953-7848
AD  - Department of Pharmacy, Sarhad University of Science & Technology, Peshawar, KPK, 
      Pakistan.
FAU - Wadood, Abdul
AU  - Wadood A
AD  - Department of Biochemistry, UCS, Shankar Abdul Wali Khan University, Mardan 
      23200, Pakistan.
FAU - Mahmood, Fawad
AU  - Mahmood F
AD  - Department of Pharmacy, Sarhad University of Science & Technology, Peshawar, KPK, 
      Pakistan.
FAU - Rashid, Umer
AU  - Rashid U
AD  - Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 
      Abbottabad 22060, Pakistan.
FAU - Ullah, Riaz
AU  - Ullah R
AD  - Department of Pharmacognosy, Medicinal, Aromatic and Poisonous Plants Research 
      Center (MAPRC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi 
      Arabia.
FAU - Sahibzada, Muhammad Umar Khayam
AU  - Sahibzada MUK
AUID- ORCID: 0000-0002-9768-4255
AD  - Department of Pharmacy, Sarhad University of Science & Technology, Peshawar, KPK, 
      Pakistan.
FAU - Alqahtani, Ali S
AU  - Alqahtani AS
AD  - Department of Pharmacognosy, Medicinal, Aromatic and Poisonous Plants Research 
      Center (MAPRC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi 
      Arabia.
FAU - Mahmood, Hafiz Majid
AU  - Mahmood HM
AUID- ORCID: 0000-0001-9215-0505
AD  - Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 
      11451, Saudi Arabia.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20200603
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Antioxidants)
RN  - 0 (Benzothiazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Glycoside Hydrolase Inhibitors)
RN  - 0 (Picrates)
RN  - 0 (Succinimides)
RN  - 0 (Sulfonic Acids)
RN  - 10X90O3503 (succinimide)
RN  - 28752-68-3 (2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid)
RN  - DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl)
RN  - EC 3.1.1.8 (Cholinesterases)
RN  - EC 3.2.1.20 (alpha-Glucosidases)
SB  - IM
MH  - Animals
MH  - Antioxidants/chemical synthesis/chemistry/*pharmacology
MH  - Benzothiazoles/analysis
MH  - Biphenyl Compounds/antagonists & inhibitors
MH  - Cholinesterase Inhibitors/chemical synthesis/chemistry/*pharmacology
MH  - Cholinesterases/metabolism
MH  - Electrophorus
MH  - Glycoside Hydrolase Inhibitors/chemical synthesis/chemistry/*pharmacology
MH  - Horses
MH  - Humans
MH  - Kinetics
MH  - *Molecular Docking Simulation
MH  - Molecular Structure
MH  - Picrates/antagonists & inhibitors
MH  - Succinimides/chemical synthesis/chemistry/*pharmacology
MH  - Sulfonic Acids/analysis
MH  - alpha-Glucosidases/metabolism
PMC - PMC7285812
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - antioxidant
OT  - cholinesterase
OT  - glucosidase
OT  - molecular docking
OT  - succinimides
COIS- The authors report no conflicts of interest in this work.
EDAT- 2020/07/02 06:00
MHDA- 2021/03/31 06:00
PMCR- 2020/06/03
CRDT- 2020/07/02 06:00
PHST- 2019/11/05 00:00 [received]
PHST- 2020/03/23 00:00 [accepted]
PHST- 2020/07/02 06:00 [entrez]
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2021/03/31 06:00 [medline]
PHST- 2020/06/03 00:00 [pmc-release]
AID - 237420 [pii]
AID - 10.2147/DDDT.S237420 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2020 Jun 3;14:2165-2178. doi: 10.2147/DDDT.S237420. 
      eCollection 2020.