含氮杂吖啶骨架的新型氨基衍生物的合成、稳定性及生物学评价

Synthesis, Stability, and Biological Evaluation of Novel Aminoderivatives Incorporating the Aza-Acridine Scaffold.

作者信息

Karelou Maria, Panara Anthi, Chatziorfanou Eleftheria, Giannopoulou Aikaterini F, Stravopodis Dimitrios J, Gikas Evagelos, Kostakis Ioannis K

机构信息

Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece.

Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece.

出版信息

Molecules. 2025 Jun 16;30(12):2612. doi: 10.3390/molecules30122612.

DOI:10.3390/molecules30122612

PMID:40572575

Abstract

Several new amino-substituted aza-acridine derivatives bearing one or two basic side chains have been designed and synthesized. Their anticancer activities were evaluated in vitro against two human cancer cell lines: T24 (urothelial bladder carcinoma, malignancy grade III) and WM266-4 (metastatic melanoma). Some of the synthesized compounds induced significant antiproliferative effects, with WM266-4 cells appearing more susceptible than T24 cells. This apparent cell-type selectivity may reflect differences in the mutational profiles and molecular target landscapes between the two cancer models. A stability study under hydrolytic conditions, based on a validated method, indicated that the most active compounds were stable under aqueous conditions. Computational analysis further supported the stability of these analogs, providing insights into the structure-stability relationships of the synthesized compounds.

摘要

设计并合成了几种带有一个或两个碱性侧链的新型氨基取代氮杂吖啶衍生物。在体外对两种人类癌细胞系进行了抗癌活性评估：T24（III级恶性膀胱尿路上皮癌）和WM266-4（转移性黑色素瘤）。一些合成化合物表现出显著抗增殖作用，WM266-4细胞似乎比T24细胞更敏感。这种明显的细胞类型选择性可能反映了两种癌症模型在突变谱和分子靶点格局上的差异。基于一种经过验证的方法进行的水解条件下的稳定性研究表明，活性最强的化合物在水性条件下是稳定的。计算分析进一步支持了这些类似物的稳定性，为合成化合物的结构-稳定性关系提供了见解。