Issue 27, 2025, Issue in Progress

Synthesis, biological activities and computational studies of bis-Schiff base derivatives of 4-hydroxyacetophenone: insights from an in vitro, molecular docking and dynamics simulation approach

Abstract

This study is based on the synthesis and acetyl and butyryl cholinesterase inhibitory activities of some bis-Schiff base derivatives of 4-hydroxyacetophenone. All the synthesized products (2a–j) were structurally analysed by means of modern spectroscopic methods, including 1H- and 13C-NMR and EI-MS, and finally tested for their ability to inhibit cholinesterase enzymes. In the series, six compounds—2j (IC50 = 15.86 ± 0.38 and 29.23 ± 0.04 μM), 2b (IC50 = 18.58 ± 0.21 and 35.31 ± 0.01 μM), 2a (IC50 = 44.36 ± 0.33 and 77.93 ± 1.46 μM), 2f (IC50 = 48.37 ± 0.06 and 76.35 ± 1.17 μM), 2g (IC50 = 62.28 ± 0.42 and 98.71 ± 1.18 μM), and 2e (IC50 = 98.21 ± 0.01 and 135.7 ± 2.61 μM)—were found to be the most promising inhibitors of acetyl and butyryl cholinesterase enzymes compared with the standard drug galantamine (IC50 = 104.8 ± 1.83 and 156.8 ± 1.83 μM), while the remaining compounds were found to be good-to-less active. Compound 2j displayed the most significant inhibition against AChE and BuChE among the tested bis-Schiff base derivatives, thus emerging as a superior compound to the standard galantamine. The highest activity of this compound is because of the favourable molecular interactions such as strong electrophilicity, high softness and a small energy gap. Molecular docking indicates that the compound 2j acts as a dual inhibitor owing to the formation of hydrophobic and polar interactions. The key structural features that include bromo benzyl and 2-methoxyphenol groups play a vital role in its efficacy, making it a more powerful inhibitor than the standard galantamine.

Graphical abstract: Synthesis, biological activities and computational studies of bis-Schiff base derivatives of 4-hydroxyacetophenone: insights from an in vitro, molecular docking and dynamics simulation approach

Supplementary files

Article information

Article type
Paper
Submitted
25 ፌብሩ 2025
Accepted
04 ጁን 2025
First published
25 ጁን 2025
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2025,15, 21700-21714

Synthesis, biological activities and computational studies of bis-Schiff base derivatives of 4-hydroxyacetophenone: insights from an in vitro, molecular docking and dynamics simulation approach

G. Badshah, A. Alam, M. Ayaz, A. A. Elhenawy, I. Ahmad, S. Ahmad, M. Usman, A. S. Alanazi, A. Latif, M. Ali and M. Ahmad, RSC Adv., 2025, 15, 21700 DOI: 10.1039/D5RA01367D

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