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Keywords:
cancer; chemical reactions; 2-methyl-1,4-naphthoquinone; quinone; synthetic platform; vitamin K
Abstract
Naphthoquinones are important natural or synthetic compounds belonging to the general class of quinones. Many compounds in this class have become drugs that are on the pharmaceutical market for the treatment of various diseases. A special naphthoquinone derivative is menadione, a synthetic naphthoquinone belonging to the vitamin K group. This compound can be synthesized by different methods and it has a broad range of biological and synthetic applications, which will be highlighted in this review.
Introduction
Naphthoquinones belong to the chemical family of quinones and are widely present in synthetic and natural products (Figure 1). In nature, quinones are biosynthesized as secondary metabolites by various organisms, from simple single-celled microorganisms to more complex beings, such as higher plants and animals [1]. Actually, quinones play important roles in several physiological processes in these organisms, such as photosynthesis [2] and oxidative phosphorylation [3,4], as well as many other metabolic processes [5-7]. Quinones also received considerable attention due to their importance in microbial systems, once several studies have shown that structural variations in microbial quinones have chemotaxonomic significance and can be used in the classification and identification of various microbial species [8]. With their particular and quite interesting chemical properties and bioactivities, naphthoquinones have aroused great interest, mainly in the pharmaceutical field, where they have been widely used in the development of new and more efficient drugs [1,9].
The naphthoquinone menadione has attracted a lot of attention. Menadione or 2-methyl-1,4-naphthoquinone (10), most known as vitamin K3, is a naphthoquinone derivative exclusively synthetic, not found in nature, used as an important precursor to synthesize vitamins K1 and K2, being classified as a provitamin (Figure 2) [10]. Vitamins K, obtained through food, play an important role in maintaining animals' physiology, by acting on blood clotting and regulating bone calcification [10]. In animals, menadione can be converted in vitamin K2 in the intestinal tract, by intestinal microbiota [10]. In humans, the menadione-vitamin K2 conversion occurs after its alkylation in the liver [11]. Moreover, in adult humans, vitamin K1 can be converted into vitamin K2, a process that requires menadione as intermediate [12]. Menadione sodium bisulfite complex (MSB, 13) [13] and menadiol (vitamin K4, 14) [14], in turn, are two...