期刊
PHARMACEUTICALS
卷 15, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ph15050541
关键词
non-small cell lung cancer; naphthoquinone; ROS; mitochondrial damage; anticancer
In this paper, the authors develop naphthoquinone derivatives with selective anticancer activity against NSCLC through a COX-2 mediated pathway. Compounds 9 and 16 demonstrate the most promising anticancer activity and show lower cytotoxicity to non-cancerous cells. Further studies are needed to understand the safety and in vivo efficacy of these compounds.
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-associated mortalities worldwide. Therefore, it is crucial to develop a novel therapeutic option targeting localized and metastatic NSCLC. In this paper, we describe the synthesis and biological activity characterization of naphthoquinone derivatives bearing selective anticancer activity to NSCLC via a COX-2 mediated pathway. The biological evaluation of compounds 9-16 showed promising structure-dependent anticancer activity on A549 cells in 2D and 3D models. Compounds were able to significantly (p < 0.05) reduce the A549 viability after 24 h of treatment in comparison to treated control. Compounds 9 and 16 bearing phenylamino and 4-hydroxyphenylamino substituents demonstrated the most promising anticancer activity and were able to induce mitochondrial damage and ROS formation. Furthermore, most promising compounds showed significantly lower cytotoxicity to non-cancerous Vero cells. The in silico ADMET properties revealed promising drug-like properties of compounds 9 and 16. Both compounds demonstrated favorable predicted GI absorption values, while only 16 was predicted to be permeable through the blood-brain barrier. Molecular modeling studies identified that compound 16 is able to interact with COX-2 in arachidonic acid site. Further studies are needed to better understand the safety and in vivo efficacy of compounds 9 and 16.
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