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An easy, efficient and one-step synthesis of the versatile, hitherto unreported of polyfunctionally substituted benzo[c][2,7]naphthyridines 4a--c is described. The reaction of 4a--c with sodium azide gives the corresponding tetracyclic ring system 6a--c in near quantitative yield, and with phenyl isothiocyanate it gives the corresponding novel 3-alkyl-2- oxo-6-phenyl-5-thioxo-3,4,5,6-tetrahydro-2H-benzo[c]pyrimido[ 4,5,6-ij][2,7]naphthyridine-1-carbonitriles 8a--c. Refl- uxing compound 4a, with alkyl amines 9a--d for 2--3 h furnished 3-alkyl-5-alkylamino-4-amino-2-oxo-2,3-dihydrobenzo[ c][2,7]naphthyridine-1-carbonitriles 10a--d, as stable crystalline solids. Compounds 10a--d reacted with acetic anhydride and triethyl orthoformate to furnish novel 3,6- dialkyl-2-oxo-3,6-dihydro-2H-benzo[c]-pyrimido[4,5,6-ij] [2,7]naphthyridine-1-carbonitriles 13a--c and 14a--c, respectively. Lastly, diazotization of 10a--c afforded the novel tetracyclic ring system 3,6-dialkyl-2-oxo-3,6-dihydro-2Hbenzo[ c][1,2,3]triazino[4,5,6-ij][2,7]naphthyridine-1-carbonitriles 16a--c. [ABSTRACT FROM AUTHOR]

Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1–6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 µM. No phenotype other than death was observed for compounds 1–3, 5, 6.

In this research, the pyridoacridines alkaloids have been docked computationally to the active site of Topoisomerase II using four PDB structures (1PVG, 1QZR, 1AJ6 and 1ZXM). iGEMDOCK 2.1, AutoDock Vina 1.1.2 and AutoDock 4.2.1 were employed to perform the automated molecular docking. The results of docking studies generated docking scores and IC values. Moreover, 3D pictures of ligand enzyme complexes afforded valuable data regarding the binding orientation of each inhibitor in the active site of Topoisomerase II. [ABSTRACT FROM AUTHOR]

Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1-6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 muM. No phenotype other than death was observed for compounds 1-3, 5, 6.