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

Gul Badshah, Aftab Alam, Muhammad Ayaz, Ahmed A. Elhenawy, Imtiaz Ahmad, Shujaat Ahmad, Muhammad Usman, Ashwag S. Alanazi, Abdul Latif, Mumtaz Ali, Manzoor Ahmad

2025RSC Advances7 citationsDOIOpen Access PDF

Abstract

= 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.

Topics & Concepts

Docking (animal)ChemistrySchiff baseIn vitroCombinatorial chemistryMolecular dynamicsComputational chemistryStereochemistryBiochemistryNursingMedicineCholinesterase and Neurodegenerative DiseasesComputational Drug Discovery MethodsSynthesis and biological activity