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Sains Malaysiana 54(9)(2025): 2201-2210
http://doi.org/10.17576/jsm-2025-5409-08
Synthesis and Evaluation of Para-Substituted Bis(Arylidene)Cycloalkanones as Potential
α-Amylase Inhibitor with Molecular Docking
and ADMET Profiling
(Sintesis dan Penilaian Para Bis(arilidena)sikloalkanon Tertukar Ganti sebagai Perencat
NUR FARAH ATIQAH AZMI1,
MOHAMAD NURUL AZMI1,*, MAHDI BABAI1,
MOHAMAD HAFIZI ABU BAKAR2, MUNTAZ ABU BAKAR3 & MOHAMMAD TASYRIQ CHE OMAR4
1Natural
Products and Synthesis Organic Laboratory (NPSO), School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
Diserahkan: 15 Mei 2025/Diterima:
18 Julai 2025
Abstract
Ten para-substituted
bis(arylidene)cycloalkanone derivatives were synthesised, characterised and
their inhibitory activities against human pancreatic α-amylase were
evaluated. Among them, halogen-substituted derivatives 5d (IC50 = 7.6 ± 1.4 µM) and 5e (IC50 = 6.9 ± 1.8 µM) exhibited
superior potency compared to the standard drug acarbose (IC50 = 23.5
± 2.7 µM). Molecular docking studies indicated that these halogenated
derivatives (i.e., compound 5d and 5e) showed a good interaction
with human pancreatic α-amylase protein (2QV4) with binding energy of -7.4
± 0.1 kcal/mol and -7.8 ± 0.1 kcal/mol, respectively, compared with acarbose
(-3.9 ± 0.1 kcal/mol). Both of them, form crucial
π–π stacking and hydrophobic interactions within the enzyme’s active
site residues TYR62 and LEU165. In silico ADMET profiling further
supported the favourable drug-likeness, synthetic accessibility, and oral
bioavailability of these compounds, making them promising candidates for
antidiabetic drug development.
Keywords: ADMET profiling; antidiabetic agents;
α-Amylase inhibitors; bis(arylidene)cycloalkanones; molecular docking
Abstrak
Sepuluh terbitan para-bis(arilidena)sikloalkanon yang tertukar ganti telah disintesis, dicirikan dan aktiviti perencatan sebatian ini terhadap enzim α-amilase pankreas manusia telah dinilai. Antaranya sebatian berhalogen, iaitu 5d (IC50 = 7.6 ± 1.4 µM) dan 5e (IC50 = 6.9 ± 1.8 µM), menunjukkan potensi perencatan yang lebih tinggi berbanding ubat piawai akarbosa (IC50 = 23.5 ± 2.7 µM). Kajian pengedokan molekul pula telah menunjukkan bahawa sebatian berhalogen (i.e., sebatian 5d and 5e) menunjukkan interaksi yang baik dengan protein α-amilase pancreas (2QV4) dengan tenaga pengikatan masing-masing -7.4 ± 0.1 kcal/mol dan -7.8
± 0.1 kcal/mol, berbanding dengan acarbose (-3.9 ± 0.1 kcal/mol). Kedua-dua sebatian ini membentuk interaksi susunan π–π dan interaksi hidrofobik yang signifikan dengan asid amino TYR62 dan LEU165 di tapak aktif enzim tersebut. Analisis ADMET secara in silico turut menyokong ciri keberkesanan ubat yang baik, kebolehcapaian sintetik dan bioketersediaan oral bagi sebatian ini, menjadikannya calon berpotensi untuk pembangunan ubat antidiabetik.
Kata kunci: Agen antidiabetik; analisis ADMET;
bis(arilidena)sikloalkanon; dok molekul; perencat
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