1,2,3-三唑和手性席夫碱杂化物作为潜在的抗癌剂：DFT、分子对接和 ADME 研究。

1,2,3-triazole and chiral Schiff base hybrids as potential anticancer agents: DFT, molecular docking and ADME studies.

机构信息

Department of Chemical Sciences, University of Johannesburg, P.O. Box 524, Auckland Park, 2006, South Africa.

Department of Biochemistry, University of Johannesburg, P.O. Box 524, Auckland Park, 2006, South Africa.

出版信息

Sci Rep. 2024 Mar 23;14(1):6951. doi: 10.1038/s41598-024-57689-5.

A series of novel 1,2,3-triazole and chiral Schiff base hybrids 2-6 were synthesized by Schiff base condensation reaction from pre-prepared parent component of the hybrids (1,2,3-triazole 1) and series of primary chiral amines and their chemical structure were confirmed using NMR and FTIR spectroscopies, and CHN elemental analysis. Compounds 1-6 were evaluated for their anticancer activity against two cancer PC3 (prostate) and A375 (skin) and MRC-5 (healthy) cell lines by Almar Blue assay method. The compounds exhibited significant cytotoxicity against the tested cancer cell lines. Among the tested compounds 3 and 6 showed very good activity for the inhibition of the cancer cell lines and low toxicity for the healthy cell lines. All the compounds exhibited high binding affinity for Androgen receptor modulators (PDB ID: 5t8e) and Human MIA (PDB ID: 1i1j) inhibitors compared to the reference anticancer drug (cisplatin). Structure activity relationships (SARs) of the tested compounds is in good agreement with DFT and molecular docking studies. The compounds exhibited desirable physicochemical properties for drug likeness.

一系列新型 1,2,3-三唑和手性席夫碱杂合体 2-6 通过席夫碱缩合反应从杂合体（1,2,3-三唑 1）的预先制备的母体成分和一系列伯手性胺合成，并通过 NMR 和 FTIR 光谱以及 CHN 元素分析确认其化学结构。通过 Almar Blue 测定法评估了化合物 1-6 对两种癌细胞 PC3（前列腺）和 A375（皮肤）和 MRC-5（健康）细胞系的抗癌活性。这些化合物对测试的癌细胞系表现出显著的细胞毒性。在测试的化合物中，化合物 3 和 6 对癌细胞系的抑制活性非常好，对健康细胞系的毒性低。与参考抗癌药物（顺铂）相比，所有化合物对雄激素受体调节剂（PDB ID：5t8e）和人 MIA（PDB ID：1i1j）抑制剂的结合亲和力都很高。测试化合物的构效关系（SARs）与 DFT 和分子对接研究非常吻合。这些化合物表现出良好的类药性物理化学性质。