Synthesis, in vitro evaluation and molecular docking studies of novel naphthoisoxazolequinone carboxamide hybrids as potential antitumor agents

Javier Maldonado, Waldo Acevedo, Aurora Molinari, Alfonso Oliva, Marcela Knox, Arturo San Feliciano

Research output: Contribution to journalArticlepeer-review

Abstract

Based on previous results with benzoindazolequinone (BIZQ) derivatives, a new series of bioisosteric 3-methylnaphtho[2,3-d]isoxazole-4,9-quinones (NIQs), conjugated with C-protected amino acids as glycine (Gly), L-alanine (Ala), L-phenylalanine (Phe) and L-glutamic acid, were synthesized from NIQ 2, and the chemical structures of intermediates and hybrids were elucidated by spectroscopic techniques. The antiproliferative activity of NIQs was evaluated by in vitro assay on cultured MCF-7 breast adenocarcinoma and KATO III gastric carcinoma cells. All the compounds showed to be cytotoxic against both cell lines, with IC50 values between 22.9 and 215.3 µM. NIQ hybrids 6, 8, and 9, conjugated with Gly, Phe and Glu, respectively, showed to be more cytotoxic, and hybrid 8 also proved to have higher activity than the precursor 2 against MCF-7 cells. Docking studies showed that NIQs exhibited very good binding energies (ΔG bin) in the active site of proteins that participate in key carcinogenic pathways.

Original languageEnglish
JournalPolycyclic Aromatic Compounds
DOIs
StateAccepted/In press - 2022
Externally publishedYes

Keywords

  • antiproliferative activity
  • bioisosteric
  • molecular docking
  • Naphthoisoxazolequinone

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