Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition.

Nocuolin A (), an oxadiazine, was isolated from the cyanobacterium sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6)-5,6-dihydro-4,6-dipentyl-2-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate () and 4-{3-[(6)-5,6-dihydro-4,6-dipentyl-2-1,2,3-oxadiazin-2-yl]-3-oxopropoxy}-4-oxobutanoic acid (), were synthesised. The chemical structures of these two compounds were elucidated by a combination of NMR and MS analysis. Compound showed cytotoxicity against the ACHN (0.73 ± 0.10 μM) and Hepa-1c1c7 (0.91 ± 0.08 μM) tumour cell lines. Similarly, compound 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 showed no in vivo toxicity in a murine model treated with a dose of 4 mg/kg body weight.