Design, synthesis, antimicrobial, antibiofilm evaluation and Z/E-isomerization of novel 6-((arylamino)methylene)benzo[a] phenazin-5(6H)-ones induced by organic solvent

Abstract

New 6-((arylamino)methylene)benzo[a]phenazin-5(6H)-one derivatives were synthesized, and good-to-high yields were achieved through one-pot, four-component condensation of 2-hydroxy-1,4-naphthoquinone, 1,2-phenylenediamine, aromatic amines and triethyl orthoformate using formic acid as catalyst under solvent-free conditions at 90 °C. The structure of these new compounds was confirmed using FT-IR and ¹H-NMR as well as MS spectroscopy. Investigation of spectroscopy data indicated that the synthesized compounds exist in the keto-enamine tautomeric form and undergo Z/E-isomerization around the CC bond in DMSO-d₆ at room temperature. Furthermore, intramolecular hydrogen bond has been observed in the synthesized E- and Z-ketoenamines. The noticeable features of the present procedure availability of starting materials, very simple operation, easy work-up, short reaction times, good to high yields and no need for column chromatography separation of benzophenazine enamines. The newly synthesized compounds were evaluated in vitro for their antibacterial, antifungal and antibiofilm activities against some of the tested microorganisms. The results demonstrated that compound 6b showed the maximum antibacterial activity, 6d exhibited the maximum antifungal activity and 6b had the most efficiency to inhibit biofilm formation of Bacillus subtilis (80%) at 200 μg mL⁻¹ concentration.