Combating pathological conditions related to hyperactivity of enzymes remains a formidable challenge for health. Small molecules therapy constitutes one of the means to circumvent the medical disorders resulting from enzyme hyperactivity. In this regard, we have synthesized structurally diverse amino acid hybrid Schiff bases (5a–5l and 10a–10k) and evaluated them for carbonic anhydrase II, α-glucosidase, and urease inhibitory potential. These new chemical scaffolds showed variable efficacies against the selected enzymes. The results indicated that compounds 5b (11.8 ± 1.33 µM), 10i (83.3 ± 1.13 µM), and 10f (88.2 ± 2.27 µM) are the most active scaffolds against carbonic anhydrase II, α-glucosidase, and urease, respectively. A structure–activity relationship revealed the most structural features contributing to the overall activities. Molecular docking suggested that these compounds possess excellent binding interactions with the active site residues of the targets by interacting through hydrogen bonding, π–π, and π–cation interactions.

与酶活性过高相关的病理状况对健康仍然是一个巨大的挑战。小分子疗法构成了规避由酶过度活跃引起的医学疾病的手段之一。在这方面，我们合成了结构多样的氨基酸杂化席夫碱（5a - 5l和10a - 10k），并对它们的碳酸酐酶II，α-葡萄糖苷酶和脲酶抑制潜力进行了评估。这些新的化学支架对选定的酶显示出不同的功效。结果表明化合物5b（11.8±1.33 µM），10i（83.3±1.13 µM）和10f（88.2±2.27 µM）分别是最有效的抗碳酸酐酶II，α-葡萄糖苷酶和脲酶的支架。构效关系揭示了构成总体活动的最结构特征。分子对接表明，这些化合物通过氢键，π-π和π-阳离子相互作用与靶标的活性位点残基具有出色的结合相互作用。