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

• Published in: Heliyon Vol. 3; no. 7; p. e00350
• Main Authors: Lateef, Mehreen, Azhar, Abid, Siddiqui, Bina S., Zarina, Shamshad, uddin, Nizam, Anwar, Muhammad F., Siddiqui, Kauser, Azhar, Kaniz F., Iqbal, Lubna, Mehmood, Rashad, Perveen, Shagufta
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2017; Elsevier
• Subjects: Biochemistry; Natural product chemistry; Organic chemistry; Organic chemistry; Biochemistry; Natural product chemistry
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2017.e00350

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 μM, respectively when compared with the standard eserine (IC50 7.8 ± 0.27 μM), 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.