Synthesis, Biological Activity, and Molecular Modelling Studies of Naphthoquinone Derivatives as Promising Anticancer Candidates Targeting COX‐2

Povilas Kavaliauskas, Felipe Stambuk Opazo, Waldo Acevedo, Ruta Petraitiene, Birutė Grybaitė, Kazimieras Anusevičius, Vytautas Mickevičius, Sergey Belyakov, Vidmantas Petraitis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Non‐small cell lung cancer (NSCLC) remains a leading cause of cancer‐associated mortal-ities 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‐de-pendent 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.

Original languageEnglish
Article number541
JournalPharmaceuticals
Volume15
Issue number5
DOIs
StatePublished - May 2022
Externally publishedYes

Keywords

  • anticancer
  • mitochondrial damage
  • naphthoquinone
  • non‐small cell lung cancer
  • ROS

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