Sains Malaysiana 50(4)(2021): 1037-1045

http://doi.org/10.17576/jsm-2021-5004-14

Cholinesterase Inhibition Activity and Molecular Docking Study of Eugenol Derivatives

(Perencatan Aktiviti Antikolinesterase dan Kajian Doking Molekul Terbitan Eugenol)

KHAIRUNISA MOHD ZAMLI¹, ASNUZILAWATI ASARI^1,2*, KOOI YEONG KHAW^3,4, VIKNESWARAN MURUGAIYAH³, MARIYA AL-RASHIDA⁵, HABSAH MOHAMAD⁶, HANIS MOHD YUSOFF^1,2, NURUL HUDA ABDUL WAHAB^1,2 & HASNAH OSMAN⁷

¹Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu Darul Iman, Malaysia

²Advanced Nano Materials (ANoMa) Research Group, Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu Darul Iman, Malaysia

³Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia

⁴Biofunctional Molecule Exploratory Research Group (BMEX), School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia

⁵Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore-54600, Pakistan

⁶Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu Darul Iman, Malaysia

⁷School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800 Penang, Malaysia

Received: 27 November 2019/Accepted: 3 September 2020

ABSTRACT

The study was conducted to explore the anticholinesterase inhibition property of eugenol derived molecules. Ten eugenol derivatives were synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by Ellman’s method. Most of the tested derivatives showed higher inhibition on BChE than AChE, however, their overall inhibitory activity was weak. In contrast, three derivatives (compounds 3,6,9) showed higher and good AChE inhibitory activity of more than 50% inhibition at 10 µg/mL. Among them, compound 9 bearing a ethyl substituent at para position of the benzoyl ring showed the most potent AChE inhibition, with IC₅₀ of 5.64 µg/mL. Ligand-protein docking simulation was also performed for the most active derived molecules (compounds 3,6,9).

Keywords: Acetylcholinesterase; butyrylcholinesterase; eugenol derivatives; molecular docking

ABSTRAK

Kajian ini dijalankan untuk mengetahui sifat perencatan antikolinesterase bagi terbitan eugenol. Sepuluh terbitan eugenol telah disintesis dan dikaji untuk aktiviti perencatan terhadap asetilkolinesterase (AChE) dan butirilkolinesterase (BChE) melalui kaedah Ellman. Kebanyakan terbitan yang diuji menunjukkan aktiviti perencatan yang lebih tinggi terhadap BChE berbanding AChE, walau bagaimanapun, secara keseluruhannya aktiviti perencatan adalah lemah. Sebaliknya, tiga terbitan (sebatian 3,6,9) menunjukkan aktiviti perencatan AChE yang tinggi dan bagus iaitu lebih daripada 50% perencatan pada 10 µg/mL. Antara sebatian tersebut, sebatian 9 yang mempunyai penukarganti etil pada kedudukan para benzena menunjukkan perencatan AChE yang paling kuat, dengan IC₅₀5.64 µg/mL. Simulasi doking protein ligan juga dilakukan untuk molekul yang paling aktif (sebatian 3,6,9).

Kata kunci: Asetilkolinesterase; butirilkolinesterase; doking molekul; terbitan eugenol

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*Corresponding author; email: asnu@umt.edu.my