Department of Chemistry, College of Science, University of Ha'il, Ha'il 81451, Saudi Arabia.
Medical and Diagnostic Research Centre, University of Ha'il, Ha'il 55473, Saudi Arabia.
Int J Mol Sci. 2024 Jan 15;25(2):1069. doi: 10.3390/ijms25021069.
To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 μg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.
为了降低癌症相关的死亡率和发病率，新型癌症治疗诊断试剂的需求很高，这也是一个新兴的研究领域。为了实现这一目标，我们报告了哌嗪连接的 1,8-萘酰亚胺-芳基磺酰衍生物（SA1-SA7）的合成和表征。这些化合物是按照两步法方案合成的，产率较高，并通过多种分析技术进行了表征。我们评估了这些化合物对非癌细胞（3T3）和乳腺癌细胞（4T1）系的体外细胞毒性和荧光细胞成像。虽然前者的研究表明这些化合物的性质安全（在 1μg/mL 时，存活率为 82-95%），但成像研究表明，设计的探针具有良好的膜通透性，可以在整个细胞质中分散。包括分子对接、分子动力学（MD）模拟和 ADME/Tox 结果在内的计算研究表明，这些化合物具有靶向表达 CAIX 的癌症的能力。这些发现表明，哌嗪连接的 1,8-萘酰亚胺-芳基磺酰衍生物是癌症治疗诊断试剂的潜在候选物，也是未来研究的有价值的骨架。
