Synthesis and evaluation of para-substituted bis(Arylidene)cycloalkanones as potential α-Amylase inhibitor with molecular docking and ADMET profiling
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...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en |
| Published: |
Penerbit Universiti Kebangsaan Malaysia
2025
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| Online Access: | http://journalarticle.ukm.my/26324/1/SMS%208.pdf http://journalarticle.ukm.my/26324/ https://www.ukm.my/jsm/english_journals/vol54num9_2025/contentsVol54num9_2025.html |
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| Summary: | 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. |
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