Piper alkamides

Piper alkamides have been reported to possess various activities, like AC AT inhibition (hyperlipidemia and atherosclerosis treatment) [220], cytotoxic [203], antimicobacterial and antibacterial [209], antifungal [210,211], insecticidal [221,222], antiprotozoan [22], anxiol3+ic, antidepressant and anti-inflammatory [23], and analgesic [20,21]. These Piper alkamides all include a characteristic methylendioxy group, which makes them inhibitors of cytochrome P450 metabohsm. 

Alkamides are responsible for the sharp, burning or tingling taste associated with herbs and spices such as prickly ash bark (Zan-thoxylum spp.), black pepper (Piper nigrum). Echinacea angustifolia, E. purpurea and cayenne (Capsicum spp.). Capsicum oleoresin contains several phenolic amides including capsaicin. 

FIGURE 4 Representative alkamides from Piper (Piperaceae). 

Decades of investigations in the natural products chemistry of the Piper genus yielded an important amount of monomeric and dimeric alkamides of diverse molecular architectures crnitributing to their biological activities [20-23,203,208-219]. Specifically, [4+2] dimers were isolated in P. chaba while [2 + 2] dimers were isolated in P. nigrum and P. longum, in both cases together with monomeric amides. 

Piperine is the major constituent found within the fruits of P. nigrum, P. longum, and many other Piper species. This natural alkamide is responsible for the taste and smell of pepper. It is estimated that each person in the United States consumes a daily intake of 21 mg of piperine [223]. Biologically, this... 

Alkamides are alkaloids of restricted distribution in plants. Although they have been isolated in more than 35 family plants, their presence is usually limited to obtain the individual alkamides in only a few milligrams. However, they are the most abundant components in Asteraceae, Solanaceae, Rutaceae, and Piperaceae families. Even within these four families, their presence is restricted to a few genera included within Anthemideae and Heliantheae tribes in Asteraceae, Capsicum in Solanaceae, Zanthoxylum and Glycosmis in Rutaceae, and Piper in Piperaceae. Stmcturally, alkamides possess an acidic and an amino moieties. Both acidic and amino moieties are characteristic depending on the plant family. 

Today, more than 300 alkamides have been isolated as natural products and more than 100 of their synthetic analogs have been prepared. A large variety of biological activities have been described for these compounds. However, three activities are predominantly important analgesic attributed to the alkenylamides isolated from some Asteraceae, Capsicum and Piper species immunomodulatory associated to the characteristic W-alkynylamides found in some of the Asteraceae plants and antifungal and insecticidal shown for the sulfurated alkamides from Glycosmis. 

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