Hassan Ahmed H E, Bayoumi Waleed A, El-Sayed Selwan M, Phan Trong-Nhat, Oh Taegeun, Ham Gyeongpyo, Mahmoud Kazem, No Joo Hwan, Lee Yong Sup
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Medicinal Chemistry Laboratory, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Pharmaceuticals (Basel). 2023 Nov 12;16(11):1594. doi: 10.3390/ph16111594.
A series of rosmarinic acid-β-amino-α-ketoamide hybrids were synthesized and rationally repurposed towards the identification of new antileishmanial hit compounds. Two hybrids, and showed promising activity (IC values of 9.5 and 8.8 μM against promastigotes, respectively). Their activities were comparable to erufosine. In addition, cytotoxicity evaluation employing human THP-1 cells revealed that the two hybrids and possess no cytotoxic effects up to 100 µM, while erufosine possessed cytotoxicity with CC value of 19.4 µM. In silico docking provided insights into structure-activity relationship emphasizing the importance of the aliphatic chain at the α-carbon of the cinnamoyl carbonyl group establishing favorable binding interactions with CALP and ARG in both hybrids and . In light of these findings, hybrids and are suggested as potential safe antileishmanial hit compounds for further development of anti-leishmanial agents.
合成了一系列迷迭香酸-β-氨基-α-酮酰胺杂合物，并对其进行合理改造，以鉴定新的抗利什曼原虫活性化合物。两种杂合物， 和 表现出有前景的活性（对前鞭毛体的IC值分别为9.5和8.8 μM）。它们的活性与依鲁替尼相当。此外，用人THP-1细胞进行的细胞毒性评估显示，两种杂合物 和 在高达100 μM时均无细胞毒性作用，而依鲁替尼具有细胞毒性，CC值为19.4 μM。计算机模拟对接提供了对构效关系的见解，强调了肉桂酰羰基α-碳上脂肪链的重要性，该脂肪链在两种杂合物 和 中与CALP和ARG建立了有利的结合相互作用。鉴于这些发现，杂合物 和 被建议作为潜在的安全抗利什曼原虫活性化合物，用于抗利什曼原虫药物的进一步开发。
