In the present paper, we report the synthesis, characterization, and biological evaluation as antifungal, antibacterial, antioxidant, and cytotoxic/anticancer agents of N-, S-, O-substituted-1,4-naphtho-and 2,5-bis(amino-substituted)-1,4-benzoquinone derivatives. In the synthesized compounds, antimicrobial activity at low concentrations against Escherichia coli B-906, Staphylococcus aureus 209-P, and Mycobacterium luteum B-917 bacteria and Candida tenuis VKM Y-70 and Aspergillus niger F-1119 fungi in comparison with controls was identified. 2-(N-Diphenylmethylpiperazin-1-yl)-3-chloro-1,4-naphthoquinone 9a was the most potent, with a minimum inhibitory concentration value of 3.9 µg/mL against test culture M. luteum. Key words quinone; antimicrobial activity; antioxidant activity; cupric-reducing antioxidant capacity method; reactive oxygen species-scavenging activity; cytotoxicity Quinonic compounds are of great importance to understand different processes that are related to biology.1) The quinone structure is common in numerous natural products that are associated with antitumor, antibacterial, antimalarial and antifungal activities.2) Furthermore, several reports have appeared in literature about anticancer activities of quinones against various cancer cell lines. [3][4][5] 1,4-Naphthoquinones are widely distributed in nature and there are many clinically important antitumor drugs containing a quinone nucleus, such as anthracyclines, mitoxantrones and saintopin, that show excellent anticancer activity. These anticancer agents are effective inhibitors of DNA topoisomerase and it is generally accepted that the cytotoxicity of quinone analogues results from the inhibition of DNA topoisomerase-II. 6) Quinone analogues can also induce the formation of semiquinone radicals, which can transfer an electron to oxygen to produce superoxide. The radical process is catalyzed by flavoenzymes such as reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome-P-450 reductase. Both the superoxide and semiquinone radical anions of naphthoquinone analogues can generate the hydroxyl radical, which is known to cause DNA strand breaks.7) Structure-activity relationship studies from quinonoid compounds indicated that the number and position of nitrogen (N) atoms substituted in the heterocyclic ring were considerably important factors to affect the biological activities. 8,9) The presence of amino, thioor chloro-moiety on the quinones was considerably important factor to effect antifungal activity. 10) Quinones, in particular naphthoquinone derivatives, have been repeatedly isolated from lower as well as higher species of plants, and are found frequently in animals. In addition to quinones possessing a biological function in cell metabolism as electron carriers, other compounds of this class have been found active against bacteria and fungi. 11,12)
