Sains Malaysiana 52(4)(2023): 1231-1242

http://doi.org/10.17576/jsm-2023-5204-15

Synthesis, Characterisation and Binding Evaluation of New 6-Amidinoindole Compound as the Potential Heme Binder

(Sintesis, Pencirian dan Penilaian Pengikatan Sebatian 6-Amidinoindol Baharu sebagai Pengikat Heme Berpotensi)

NORAISYAH ABDUL KADIR JILANI¹, NATSUHISA OKA^2,3, KAORI ANDO² & SITI AISHAH HASBULLAH^1,*

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

²Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan

³Institute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, Japan

Received: 11 March 2022/Accepted: 6 March 2023

Abstract

In this study, the new compound 6-amidinoindole 3 were synthesized by hydrogenating the amidoxime unit in a high yield. The compound was characterized by FTIR, ¹H NMR, ¹³C NMR and ESI-MS. The binding of the compound towards heme was evaluated using absorption spectroscopy. The studies found that the association constant (log K) is 3.90. The binding strength indicated the ligand's possibility to interact significantly with heme and acted as a binder to the malaria parasite. In silico hemozoin docking was performed to gain insight into the mode of action. The docked score is -8.3 kcal/mol, indicated the possible inhibition of hemozoin. This study could serve as the basis for the future development of malaria sensors and antiplasmodial activity.

Keywords: Amidino; heme binding; indole; malarial molecular target; synthesis

Abstrak

Dalam kajian ini, sebatian 6-amidinoindol 3 baharu telah disintesis melalui penghidrogenan unit amidoksim dan hasil yang tinggi telah diperoleh. Sebatian ini telah dicirikan oleh FTIR, ¹H NMR, ¹³C NMR dan ESI-MS. Pengikatan sebatian terhadap heme telah dinilai menggunakan spektroskopi serapan. Kajian mendapati bahawa pemalar pengikatan (log K) ialah 3.90. Kekuatan pengikatan menunjukkan kebolehan ligan berinteraksi dengan heme secara signifikan dan juga bertindak sebagai pengikat kepada parasit malaria. Mengedok hemozoin secara in silico dilakukan untuk mendapatkan gambaran lebih dalam tentang cara kerja. Dok skor ialah -8.3 kcal/mol yang menunjukkan kemungkinan berlakunya perencatan hemozoin. Kajian ini boleh menjadi asas untuk pembangunan sensor malaria dan aktiviti antiplasmodial pada masa hadapan.

Kata kunci: Amidino; indol; pengikatan heme; sasaran molekul malaria; sintesis

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_*Corresponding author; email: aishah80@ukm.edu.my