Design, Synthesis, Biological Evaluation, and Antioxidant and Cytotoxic Activity of Heteroatom-Substituted 1,4-Naphtho- and Benzoquinones

Abstract

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)

Synthesis, Antimicrobial Properties, and Inhibition of Catalase Activity of 1,4-Naphtho- and Benzoquinone Derivatives Containing N-, S-, O-Substituted

“…Thus, exclusively 2-and/or 2,5-isomer were formed due to electrostatic reasons for compounds 17-25. The results agree well with the corresponding mechanism in the similar compounds [6,26].…”

“…Natural and synthetic quinonoid compounds are well-known substances which possess a variety of biological properties such as anticancer, antibacterial, or antimalarial drugs as well as fungicides [1]. The heterocyclic derivatives of 1,4naphthoquinones have been identified that have potent biological activities towards viral [2], molluscicidal [3], malarial [4], leishmanial [5], cancer [6], and bacterial and fungal diseases [7] due to their redox potentials [8]. Some of these pharmacological effects have been attributed to the formation of DNA-damaging anion-radical intermediates formed by bioreduction of the quinone nucleus.…”

“…As a part of a program directed towards the design and synthesis of N-, S-, O-substituted quinones as potential antibacterial, antifungal, and anticancer agents, we have reported the synthesis and antimicrobial as well as anticancer activities of N-, S-, O-substituted quinones [6,9,10]. This paper describes the synthesis, characterization, and discovering promising pharmacologically active compounds.…”

A method for dyeing polyester fibres with quinone derivatives and evaluation of their antioxidant activity

“…The naphthoquinone scaffold was an important pharmacophore found in a large number of biologically active compounds [7]. N-, S-, O-substituted-1,4-naphthoquinones are also reported to have good biological properties [8].…”

Synthesis and Antimicrobial Activity of 1,4-Naphthoquinones Derivatives with [1,2,4]-Triazole-3-thione Substitution

“…Antibacterial and antifungal activity of S,Ncontaining derivatives of quinones has been studied in our laboratory previously [12,13] . Depending on the substituent, the results of antimicrobial activity of synthesized compounds differed in the degree of influence on bacteria and fungi.…”