Sains Malaysiana 49(8)(2020): 1905-1913

http://dx.doi.org/10.17576/jsm-2020-4908-12

Molecular Docking Study of the Interactions between Plasmodium falciparum Lactate Dehydrogenase and 4-aminoquinoline Hybrids

(Kajian Dok Molekul Mengenai Interaksi antara Hibrid 4-aminokuinolina dan Plasmodium falciparum Laktat Dehidrogenase)

NUR HANIS ZAKARIA¹, LAM KOK WAI² & NURUL IZZATY HASSAN¹* 

¹Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

²Drug and Herbal Research Centre, Faculty of Health Sciences, Universiti Kebangsaan Malaysia

Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

Received: 29 January 2020/Accepted: 10 April 2020

Abstract

Malaria is a potentially deadly disease with many anti-malarial drugs have been rendered ineffective due to Plasmodium falciparum resistance concern. Plasmodium falciparum lactate dehydrogenase (PfLDH) enzyme is a crucial malaria parasite enzyme involved in the glycolytic pathway, thus, has been considered as a potential molecular target. Initially, molecular docking was performed using AutoDock Vina, Molegro Virtual Docker, and CDOCKER software to investigate the molecular interactions of 4-aminoquinoline antimalarial hybrids compounds with PfLDH enzyme. All ten 4-aminoquinoline hybrids derivatives docked to the PfLDH binding site. The results showed that these compounds exhibited either comparable or higher binding affinity than the reference drug chloroquine, amodiaquine, and hydroxychloroquine. Visually, some of the compounds possessed functional binding interactions, possibly due to their similar structural conformation and binding interactions of chloroquine in the binding site. Apart from that, the docking results also suggest that these compounds potentially promote additional hydrogen-bonding interactions with the residues in the binding site. Interestingly, the compounds also predicted to interact with essential PHE52, VAL26, ILE54, ILE119, and ALA98 residues, which are required to act as a competitive inhibitor for this glycolytic enzyme.

Keywords: 4-aminoquinoline; malaria; molecular docking; Plasmodium falciparum lactate dehydrogenase (PfLDH) enzyme

Abstrak

Malaria merupakan antara penyakit yang boleh menyebabkan kematian dengan peningkatan kerintangan ubat-ubatan anti-malaria sedia ada. Enzim Plasmodium falciparum dehidrogenase (PfLDH) merupakan enzim sasaran yang terlibat dalam laluan glikolitik. Oleh itu, kajian dok molekul telah dijalankan menggunakan perisian AutoDock Vina, Molegro Virtual Docker dan CDOCKER untuk mengkaji interaksi molekul antara 4-aminokuinolina antimalaria hibrid terhadap PfLDH enzim. Kesemua sepuluh sebatian hibrid dilihat sesuai untuk didok menggunakan kedua-dua perisian dan menunjukkan pengikatan keafinan yang baik dan setanding dengan pengikatan keafinan sebatian klorokuina, amodiakuina dan hidrosiklorokuina. Pengikatan keafinan yang baik dan setanding klorokuina disebabkan persamaan struktur bentuk dengan klorokuina pada tapak pengikat selain kemampuan menambah ikatan hidrogen. Sebatian juga berinteraksi dengan asid amino yang penting sebagai perencat bersaing untuk enzim glikolitik. Semua asid amino yang penting termasuklah PHE52, VAL26, ILE54, ILE119 dan ALA98.

Kata kunci: Dok molekul; enzim Plasmodium falciparum dehidrogenase (PfLDH); malaria; 4-aminokuinolina

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*Corresponding author; email: drizz@ukm.edu.my