Anticancer compounds quinones

Examples of activated double bond electrophiles include a, 3-unsaturated carbonyl compounds, quinones, quinoneimines, quinonemethides and diiminoquinones as shown in Fig. 10.32B. These electrophilic intermediates are highly polarized and can react with nucleophiles in a 1,4-Michael-type addition at the more electrophilic or 3-oarbon of the activated double bond intermediate to the addition product (Fig. 10.32A). Specific examples of activated double bond electrophiles that have been proposed for the anticancer drug leflunamide, the food antioxidant butylated hydroxytoluene, acetaminophen, the antiandrogen flutamide, the anticonvulsant felbamate and the cytotoxic cyclophosphamide as shown in Fig. 10.32C. The bioinaotivation pathways for these electrophilic intermediate can involve either direct addition, with or without transferases, depending upon the degree of polarization and reactivity of the electrophilic intermediate (hard vs soft electrophiles). 

In connection with a study of a number of anticancer compounds which, presumably also act as inhibitors of free-radical polymerization, eight classes of compounds were studied as to their inhibitory properties. The classes studied were unsaturated hydrocarbons, phenolic compounds, quinones, amines, stable free-radicals, sulfiir compounds, carbonyl compounds, and metallic salts. The most effective inhibitors, of those evaluated, were cupric acetate and cupric resinate, followed by /runs-1,3,5-hexatriene, hydroquinone, benzoquinone, and diphenylamine as modest inhibitors. Among the low-activity inhibitors were 2,2-diphenyl-1-picrylhydrazyl, benzene thiol, and crotonaldehyde [70]. 

There are various pathways for free radical-mediated processes in microsomes. Microsomes can stimulate free radical oxidation of various substrates through the formation of superoxide and hydroxyl radicals (the latter in the presence of iron) or by the direct interaction of chain electron carriers with these compounds. One-electron reduction of numerous electron acceptors has been extensively studied in connection with the conversion of quinone drugs and xenobiotics in microsomes into reactive semiquinones, capable of inducing damaging effects in humans. (In 1980s, the microsomal reduction of anticancer anthracycline antibiotics and related compounds were studied in detail due to possible mechanism of their cardiotoxic activity and was discussed by us earlier [37], It has been shown that semiquinones of... 

Many organic and inorganic compounds, fibers, and particles are capable of damaging nucleic acids by generating reactive oxygen species via the reduction of dioxygen. These stimuli include different classes of organic compounds, classic prooxidants (anticancer antibiotics, various quinones, asbestos fibers, and so on), and even antioxidants, which can be oxidized in the presence of transition metal ions. 

The sulfur compound sulfuraphane, extracted from fresh broccoli, has received attention in recent years because of its strong action in inducing synthesis of quinone reductase and glutathione S-transferases that help detoxify xenobiotics and may have significant anticancer activity/... 

The anticancer activity and host toxicity of compounds with a quinone group was investigated. There is considerable death of tumour cells, together with the induction of breaks in DNA single and double strands, although a low binding value for the semiubiquinone with DNA was found [132]. 

Naturally-occurring quinones of the naphthoquinone group also exert potent antineosplastic activity, and it is interesting highlight that the most studied compound is lapachone, Fig. (7). Pyranonaphthoquinones such as a-and P-lapachone have diverse biological activities and there has recently also been an increased interest in their anticancer activity. P-Lapachone, a plant... 

Red sandalwood Pterocarpus santalinus has attracted interest as a colourant and contains the colourless components, pterostilbene (34), pterocarpin (35) and homopterocarpin (36) the occurrence of which (ref. 101)and the chemistry (ref. 102) have been reviewed. The nature of the possible involvement of these compounds in the development of colour in sandalwood is not known although quinone and quinone dimer structures seem highly probable. Pterostilbene is the dimethyl ether of resveratrole, a natural widely-occurring phenolic component of many plants including grapes, mulberries and peanuts. The anticancer properties (ref. 103) and beneficial effect on coronary heart disease of this have been intensively studied recently (ref 104). ... 

S. Shaaban, R. Diestel, B. Hinkelmann, Y. Muthukumar, R. P. Verma, F. Sasse, C. Jacob, Eur. J. Med. Chem. 2012, 58, 192-205. Novel peptidomimetic compounds containing redox active chalcogens and quinones as potential anticancer agents. 

In this paper further optimisation of the HPLC-system with the SMDE-detector will be reported. As a test compound the anticancer agent mitomycin C has been used, containing an easily reducible quinone-structure. For this compound, an HPLC-assay in plasma with U.V-detection has already been worked out[22], while the electrochemistry has been studied extensively[23]. 

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