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Sains Malaysiana 53(8)(2024): 1969-1980
http://doi.org/10.17576/jsm-2024-5308-19
Insight into the in silico Study and Biological Evaluation of
Curcumin Analogue Compounds as New Potential Inhibitors for Dengue DEN2
NS2B/NS3 Serine Protease
(Kajian in silico dan Penilaian Biologi Sebatian Analog Kurkumin sebagai Perencat Baharu yang Berpotensi untuk Serin Protease Denggi DEN2
NS2B/NS3)
NENI FRIMAYANTI1,*, NOVAL HERFINDO1, SITI AISYAH2 & ENI NUR RAHMAWATY2
1Sekolah Tinggi Ilmu Farmasi Riau, Pekanbaru, Indonesia
2Department of Chemistry, Faculty of Mathematic and
Natural Products, Universitas Riau, Kampus Bina Widya KM. 12,5, Simpang Baru, Kec. Tampan, Kota Pekanbaru, Riau 28293
Diserahkan: 10 Januari 2024/Diterima: 12 Jun 2024
Abstract
Dengue
is an infectious disease caused by a virus and it is a rapidly emerging
pandemic disease in many parts of the
world. However, to date, one licensed tetravalent Dengvaxia vaccine based on a yellow fever virus vaccine
variant has been reported. In silico and biological assay were performed to twenty two curcumin analogue compounds with DEN2
NS2B/NS3 serine protease as target. The main purpose of
this study were to predict and estimate the binding interaction and also
the ability of curcumin analogue compounds to be potential inhibitors
for DEN2 NS2B/NS3. Computational pipeline
such as molecular docking and molecular dynamic were constructed to get insight
into potential inhibitor for DEN2 NS2B/NS3. Biological assay was performed to
validate in silico results. Docking
results reported that compounds 3, 10, and 13 have the lowest binding
free energy value of -15.2 kcal/mol, -13.66 kcal/mol and -13.68 kcal/mol,
respectively. All these three compounds were also able to interacts with Lys74
(i.e., allosteric site of serine protease) through hydrogen bonding, these binding is
keep maintain during the molecular dynamic simulation. Among all of the
compounds tested on their percent inhibition against DEN2 NS2B/NS3, compounds 3, 10, and 13 exhibited
the best of percent inhibition. Thus, three of these compounds can be used as
potential candidate for the next stage in the drug discovery process.
Keywords: ADME; curcumin; dengue DEN2 NS2B/NS3; docking; molecular dynamic
Abstrak
Denggi ialah penyakit berjangkit yang disebabkan oleh virus dan ia merupakan penyakit pandemik yang cepat muncul di seluruh bahagian dunia. Namun setakat ini, hanya satu vaksin tetravalen yang berlesen, Dengvaxia,
yang berdasarkan varian vaksin virus demam kuning yang telah dilaporkan. In
silico dan ujian biologi telah dilakukan kepada dua
puluh dua sebatian analog kurkumin dengan DEN2 NS2B/NS3 serine protease sebagai
sasaran. Tujuan utama kajian ini adalah untuk meramal dan menganggar interaksi
pengikatan dan juga keupayaan sebatian analog kurkumin menjadi perencat yang
berpotensi untuk DEN2 NS2B/NS3. Saluran paip pengiraan seperti dok molekul dan
dinamik molekul telah dibina untuk mendapatkan pandangan tentang potensi
perencat untuk DEN2 NS2B/NS3. Ujian biologi dilakukan untuk mengesahkan
keputusan in silico. Keputusan dok melaporkan bahawa sebatian 3, 10 dan 13 mempunyai nilai tenaga bebas pengikatan terendah
masing-masing -15.2 kcal/mol, -13.66 kcal/mol dan -13.68 kcal/mol. Ketiga-tiga
sebatian ini juga dapat berinteraksi dengan Lys74 (iaitu tapak alosterik
protease serin) melalui ikatan hidrogen, pengikatan ini dikekalkan semasa
simulasi dinamik molekul. Antara semua sebatian yang diuji pada perencatan
peratus mereka terhadap DEN2 NS2B/NS3, sebatian 3, 10 dan 13 menunjukkan perencatan peratus terbaik. Oleh itu, tiga daripada sebatian ini
boleh digunakan sebagai calon berpotensi untuk peringkat seterusnya dalam
proses penemuan dadah.
Kata kunci: ADME; denggi DEN2 NS2B/NS3;
dinamik molekul; dok; kurkumin
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*Pengarang untuk surat-menyurat;
email: nenifrimayanti@gmail.com
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