Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition
2023
Víctor Tena Pérez | Luis Apaza Ticona | Alfredo H. Cabanillas | Santiago Maderuelo Corral | Diego Fernando Rosero Valencia | Antera Martel Quintana | Montserrat Ortega Domenech | Ángel Rumbero Sánchez
Nocuolin A (<b>1</b>), an oxadiazine, was isolated from the cyanobacterium <i>Nostoc</i> sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6<i>R</i>)-5,6-dihydro-4,6-dipentyl-2<i>H</i>-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate (<b>2</b>) and 4-{3-[(6<i>R</i>)-5,6-dihydro-4,6-dipentyl-2<i>H</i>-1,2,3-oxadiazin-2-yl]-3-oxopropoxy}-4-oxobutanoic acid (<b>3</b>), were synthesised. The chemical structures of these two compounds were elucidated by a combination of NMR and MS analysis. Compound <b>3</b> showed cytotoxicity against the ACHN (0.73 ± 0.10 μM) and Hepa-1c1c7 (0.91 ± 0.08 μM) tumour cell lines. Similarly, compound <b>3</b> significantly decreased cathepsin B activity in ACHN and Hepa-1c1c7 tumour cell lines at concentrations of 1.52 ± 0.13 nM and 1.76 ± 0.24 nM, respectively. In addition, compound <b>3</b> showed no in vivo toxicity in a murine model treated with a dose of 4 mg/kg body weight.
显示更多 [+] 显示较少 [-]