Dewick P.M. Medicinal natural products VCH-Wiley, Weinheim, 2002 / booktext@id88013692placeboie

Figure 6.27

Figure 6.29

glyceraldehyde

Figure 6.30

Vitamin B3

Vitamin B3 (nicotinic acid, niacin) (Figure 6.28) is a stable water-soluble vitamin widely distributed in foodstuffs, especially meat, liver, fish, wheat germ, and yeast. However, in some foods, e.g. maize, it may be present in a bound form, and is not readily available. Diets based principally on maize may lead to deficiencies. The amino acid tryptophan can be converted in the body into nicotinic acid (Figure 6.29), and may provide a large proportion of the requirements. Nicotinic acid is also produced during the roasting of coffee from the decomposition of the N-methyl derivative trigonelline (Figure 6.28). Nicotinic acid is converted into nicotinamide (Figure 6.28), though this compound also occurs naturally in many foods. The term vitamin B3 is often used for the combined nicotinamide–nicotinic acid complement. In the form of the coenzymes NAD+ and NADP+, nicotinamide plays a vital role in oxidation–reduction reactions (see page 24), and is the most important electron carrier in primary metabolism. Deficiency in nicotinamide leads to pellagra, which manifests itself in diarrhoea, dermatitis, and dementia. Oral lesions and a red tongue may be more noticeable than the other symptoms. Nicotinamide is usually preferred over nicotinic acid for dietary supplements since there is less risk of gastric irritation. Both are produced synthetically. It is common practice to enrich many foods, including bread, flour, corn, and rice products.

Nicotinic acid in large doses can lower both cholesterol and triglyceride concentrations by inhibiting their synthesis.

NADP+

Figure 6.31

Figure 6.33

Tobacco

Tobacco is the cured and dried leaves of Nicotiana tabacum (Solanaceae), an annual herb indigenous to tropical America, but cultivated widely for smoking. Tobacco leaves may contain from 0.6–9% of (−)-nicotine (Figure 6.28), an oily, volatile liquid alkaloid, together with smaller amounts of structurally related alkaloids, e.g. anabasine and nornicotine (Figure 6.28). In the leaf, the alkaloids are typically present as salts with malic and citric acids. Nicotine in small doses can act as a respiratory stimulant, though in larger doses it causes respiratory depression. Despite the vast array of evidence linking tobacco smoking and cancer, the smoking habit continues throughout the world, and tobacco remains a major crop plant. Tobacco smoke contains a number of highly carcinogenic chemicals formed by incomplete combustion, including benzpyrene, 2-naphthylamine, and 4-aminobiphenyl. Metabolism by the body’s P-450 system leads to further reactive intermediates, which can combine with DNA and cause mutations. Tobacco smoking also contributes to atherosclerosis, chronic

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bronchitis, and emphysema, and is regarded as the single most preventable cause of death in modern society. Nicotine is being used by former smokers who wish to stop the habit. It is available in the form of chewing gum or nasal sprays, or can be absorbed transdermally from nicotine-impregnated patches.

Figure 6.34

Powdered tobacco leaves have long been used as an insecticide, and nicotine from Nicotiana tabacum or N. rustica has been formulated for agricultural and horticultural use. The free base is considerably more toxic than salts, and soaps were included in the formulations to ensure a basic pH and to provide a surfactant. Other Nicotiana alkaloids, e.g. anabasine and nornicotine, share this insecticidal activity. Although an effective insecticide, nicotine has been replaced by other agents considered to be safer. Nicotine is toxic to man due to its effect on the nervous system, interacting with the nicotinic acetylcholine receptors, though the tight binding observed is only partially accounted for by the structural similarity between acetylcholine and nicotine (Figure 6.34). Recent studies suggest that nicotine can improve memory by stimulating the transmission of nerve impulses, and this finding may account for the lower incidence of Alzheimer’s disease in smokers. Any health benefits conferred by smoking are more than outweighed by the increased risk of heart, lung, and respiratory diseases.

Areca

Areca nuts (betel nuts) are the seeds of Areca catechu (Palmae/Arecaceae), a tall palm cultivated in the Indian and Asian continents. These nuts are mixed with lime, wrapped in leaves of the betel pepper (Piper betle) and then chewed for their stimulant effect, and subsequent feeling of well-being and mild intoxication. The teeth and saliva of chewers stain bright red. The major stimulant alkaloid is arecoline (up to 0.2%) (Figure 6.36), the remainder of the alkaloid content (total about 0.45%) being composed of related reduced pyridine

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316 ALKALOIDS

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structures, e.g. arecaidine, guvacine (tetrahydronicotinic acid), and guvacoline (Figure 6.36).

Figure 6.36