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New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, in vitro and in silico studies.

ABSTRACT: To treat Alzheimer's disease (AD), the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (2-8) were synthesized by the reaction of anthrarobin (1) and acetic anhydride/acyl chlorides. The product were characterized by 1H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE) inhibition activity. Compounds 5 and 4 showed notable BuChE inhibitory potential with IC50 5.3 ± 1.23 and 17.2 ± 0.47 ?M, respectively when compared with the standard eserine (IC50 7.8 ± 0.27 ?M), compound 5 showed potent BuChE inhibition potential than the standard eserine. The active compounds 5 and 4 have acyl groups at 2-OH and 10-OH positions which may be responsible for inhibitory potential as this orientation is absent in other products. In silico studies of 5 and 4 products revealed the high inhibitory potential due to stable binding of ligand with the BuChE active sites with docking energy score -18.8779 kcal/mol and -23.1159 kcal/mol, respectively. Subsequently, compound 5 that have potent BuChE inhibitory activity could be the potential candidate for drug development for Alzheimer's disease.

SUBMITTER: Lateef M

PROVIDER: S-EPMC5506883 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, in vitro and in silico studies.

Lateef Mehreen M Azhar Abid A Siddiqui Bina S BS Zarina Shamshad S Uddin Nizam N Anwar Muhammad F MF Siddiqui Kauser K Azhar Kaniz F KF Iqbal Lubna L Mehmood Rashad R Perveen Shagufta S

Heliyon 20170710 7

To treat Alzheimer's disease (AD), the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (2-8) were synthesized by the reaction of anthrarobin (1) and acetic anhydride/acyl chlorides. The product were characterized by 1H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE) inhibition activi ...[more]

PMID: 28725871

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New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, in vitro and in silico studies.

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New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, <i>in vitro</i> and <i>in silico</i> studies.

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