Synthesis of symmetrical and asymmetrical azines from hydrazones and/or ferrocenecarboxaldehyde as potential antimicrobial–antitumor agents

Abstract

9-Fluorenone azine 2a and benzophenone azine 2b were synthesized, respectively, by treatment of 9-fluorenone hydrazone 1a or benzophenone hydrazone 1b with FeCl3 in chloroform. Ferrocenecarboxaldehyde 3 reacts with 1a or 1b, in ethanol, to furnish novel asymmetrical azine products 1-((ferrocenyl)methylene)-2-(9H-fluoren-9-ylidene)hydrazine 3a or 1-((ferrocenyl)methylene)-2-(diphenylmethylene)hydrazine 3b, respectively. The compounds were characterized by IR,1H, 13C and DEPT-135 NMR spectroscopy, high resolution ESI+-MS or EI, and also by single crystal X-ray diffraction analysis (in the case of 2b and 3b). The contribution of the azine functional group (3a) in the LUMO orbital was justified by observing a red shift in the MLCT upon its protonation. The antimicrobial activities of 2a, 2b, 3a and 3b were determined against some Gram-positive and Gram-negative bacteria in addition to Candida albicans and Aspergillus niger using paper disc diffusion method. Moderate antibacterial activities were found for 3a and 3b while weak activities were recorded for 2a and 2b compared to Ampicillin, positive control. No antifungal or antitumor activities were found for all the tested compounds, except 3a which showed antitumor activity. Low toxicity was recorded for 3a and 3b using Artemia salina as test organism. Hence, the prepared products 3a and 3b can be used as antimicrobial agents due to their antibacterial activities and low cell toxicity.