*3.1.1 Hemiterpenes*

Hemiterpenes are part of minor terpenes of EOs. They are usually alcohols, aldehydes, and esters, with a 2-methylbutane skeleton [131]. The number of

*Structures of some monoterpenes and monoterpenoids.*

#### *Essential Oils - Bioactive Compounds, New Perspectives and Applications*

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*3.1.2 Monoterpenes*

*Structures of some diterpenes and diterpenoids.*

**Figure 17.**

*Terpenoids as Important Bioactive Constituents of Essential Oils DOI: http://dx.doi.org/10.5772/10.5772/intechopen.91426*

hemiterpene aglycone is less than 100 [132]. Chlorinated hemiterpenes were

Regular monoterpenes are made from the combination of two isoprene units (C10) linked by the head-to-tail binding. They are the major molecules consisting of 90% of (some) EOs; thereby, they contribute to the specific smell of plants [134, 135]. Monoterpenes are found in nearly all EOs and usually possess one double bond in their structures. In nature, they are mostly involved in plant– animal and plant–plant interactions such as pollination, seed and fruit dissemination, and allelopathic agents. Monoterpenes occur in more than 30 known

recently isolated from the leaves of *Prinsepia utilis* (**Figure 14**) [133].

**Figure 16.** *Structures of some sesquiterpenes and sesquiterpenoids.*

*Terpenoids as Important Bioactive Constituents of Essential Oils DOI: http://dx.doi.org/10.5772/10.5772/intechopen.91426*

*Essential Oils - Bioactive Compounds, New Perspectives and Applications*

**90**

**Figure 16.**

*Structures of some sesquiterpenes and sesquiterpenoids.*

**Figure 17.** *Structures of some diterpenes and diterpenoids.*

hemiterpene aglycone is less than 100 [132]. Chlorinated hemiterpenes were recently isolated from the leaves of *Prinsepia utilis* (**Figure 14**) [133].

#### *3.1.2 Monoterpenes*

Regular monoterpenes are made from the combination of two isoprene units (C10) linked by the head-to-tail binding. They are the major molecules consisting of 90% of (some) EOs; thereby, they contribute to the specific smell of plants [134, 135]. Monoterpenes are found in nearly all EOs and usually possess one double bond in their structures. In nature, they are mostly involved in plant– animal and plant–plant interactions such as pollination, seed and fruit dissemination, and allelopathic agents. Monoterpenes occur in more than 30 known

skeletons and can be divided into 3 subgroups: acyclic, monocyclic, and bicyclic. A number of monoterpenes are oxygenated (**Figure 15**).

#### *3.1.3 Sesquiterpenes*

Sesquiterpenes are other major EO components and are less volatile than monoterpenes. They are derived from three isoprene units and exist in a wide variety of forms, including linear, monocyclic, bicyclic, and tricyclic frameworks. Sesquiterpenes are the most diverse group of terpenoids (**Figure 16**).

#### *3.1.4 Diterpenes*

They are chemically complex and are usually components of plants resins but are sometimes encountered as by-products in the isolation of EOs. Diterpenes are less volatile because of their high molecular weights and less numerous than the monoand sesquiterpenes. Consequently, they are difficult to extract by steam distillation and then appear rarely in distilled EOs. When present, they are found in EOs in very low amounts. However, traditional extraction using distillation allows separation and identification of diterpenes present in EOs [136]. Generally, molecules with molecular masses higher than 300 uma can be seen as sign of improper extraction conditions or adulteration. Diterpenes that are usually found in EOs include camphorene, cafestol, kahweol, cambrene, and taxideme (**Figure 17**).

#### **3.2 Bioactivities of terpenoids**

Some sesquiterpenoids are very toxic, but some are antifungals, carminatives, and insecticides.

Being complex mixtures of constituents, overall activities of EOs cannot therefore be attributed only to their major components (terpenoids) [137]. Many aroma components of EOs, such as terpenes and terpenoids, were proposed to contribute to their antioxidant activity; that include *β*-terpene and *β*-terpinolene in *Melaleuca alternifolia*, 1,8-cineole in *Mentha aquatic*, and linalool in black cumin. Less volatile but strongly bitter-tasting or toxic terpenes also protect some plant from being eaten by animals. Some terpenes are potent drugs against diseases such as heart disease, malaria, and cancer [34].

## **4. Importance of terpenes terpenoids found in essentials oils**

Terpenoids are, by far, the most important group (numerous and structurally diverse) of natural products as far as EOs are concerned. Reports on the level of terpenoids in EOs vary considerably. Many terpenes have biological activities and are used for medical purposes. For example, the antimalarial drug artemisinin and the anticancer drug Taxol (paclitaxel) are two of a few terpenes with established medical applications [26].

Monoterpenes are well known as main constituents of EOs, floral, and scents. Monoterpenes and monoterpenoids have antioxidant, anticonvulsant, antiulcer, anti-inflammatory, antiseptic, antitumor, antiviral, analgesic, antihypertensive, antibacterial, and therapeutic antidiabetic properties [26, 138]. The general mechanism of action of monoterpenes, such as their antimicrobial and antitussive activity, is mainly related to their volatility. Their hydrophobicity, as well as the EOs as a whole, determines their effect on bacterial cell structures with a subsequent antimicrobial effect [139]. *α*-Terpineol is used to enhance skin penetration and

**93**

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rich in monoterpenes has been established experimentally [149].

alcohol inhibitions were weak [150].

lol, and myrcene [152, 153].

Some bicyclic monoterpenoids are known to suppress the acetylcholinesterase activity, which is increased in patient with Alzheimer's disease. In a study of 17 monoterpenes and monoterpenoids, (+)- and (−)-*α*-pinene and (+)-3-carene appeared as potent inhibitors of the enzyme AChE, while the bicyclic ketones and

In recent years, a considerable large number of research studies have been carried out on the chemical constituents of EOs as source of bioactive natural products

Many EO components possess enantiomers that can be sometime present in an oil. It is important to note that there is a close relationship between the chirality of organic compounds and their biological properties. For a given optically active substance, the activity is not identical for both enantiomers [153]. Linalool, for example, has two enantiomers: (3*S*)-(+)-linalool known as coryandrol and (3*R*)-(−)-linalool known as licareol. Both have distinct properties. It was reported that although (*S*)-(+)- and (*R*)-(−)- have similar activity profiles, the effect of (*R*)-(−)-linalool is more intense [154]. Similarly, De Sousa and coworkers showed that regarding the anticonvulsant activity, (*R*)-(−)-linalool and the racemate form were more active than the (*S*)-(+)- enantiomer, which had effects compatible with

Geraniol, an acyclic aldehyde monoterpene present in various EOs from many aromatic plants, has in vitro and in vivo antitumor activity against several cancer cell lines. In fact, geraniol alters several metabolic pathways of HepG2 cells such

against cancer. Piaru and collaborators showed that EO of *Myristica fragrans* exhibited good cytotoxic activity, possibly due to the presence of some potential anticancer substances such as limonene, terpinen-4-ol, eugenol, and myristicin [151]. Similarly, EO from *Vepris macrophylla* demonstrated a strong cytotoxic effect, which may be attributed to the presence of specific components like citral, citronel-

diazepam and phenytoin, known as anticonvulsant agents [148, 153].

also has insecticidal properties [140]. Monoterpenes have been shown to exert chemopreventive as well as chemotherapeutic activities in mammary tumor models and thus may represent a new class of therapeutic agents [138]. The EO of *Melissa officinalis* L. can inhibit the replication of HSV-2, due to the presence of citral and citronellal [141]. Linalool is an unsaturated alcohol monoterpene found as principal constituent in many EOs known to exhibit various biological activities that include antibacterial, antiplasmodial, and antinociceptive effects in different animal models [142–144]. Linalool also plays an important role in nature as a key compound in the complex pollination biology of various plant species to ensure reproduction and survival. It is also a key compound for the industrial production of a variety of fragrance chemicals such as geraniol, nerol, citral and its derivatives, as well as a lead compound in the synthesis of vitamins A and E. Its repellent properties on various crop-destroying insects are well studied and documented, hence accentuating the application of linalool in eco-friendly pest management [145]. In Malaysia, linalool is reported to be the major component of EOs of different aromatic species of the Lauraceae family; hence it may be classified as a taxon of this family [146]. Limonene is among the most abundant monoterpene constituents found in nature, and it occurs in a variety of trees and herbs that include *Citrus* species. It has been an interesting target molecule for chemists and biologists. Limonene inhibits LPS-induced NO and PGE2 production that included dose-dependent decreases in the expression of iNOS and COX-2 proteins [147]. Some in vitro and in vivo studies have revealed the effects of monoterpenes on diabetes, insulin resistance, and obesity. The role of inflammation as a link between diabetes and obesity has been established. Many monoterpenes exhibit ameliorative effects in inflammatory conditions associated with diabetes [148]. The analgesic effect of many plant EOs

#### *Terpenoids as Important Bioactive Constituents of Essential Oils DOI: http://dx.doi.org/10.5772/10.5772/intechopen.91426*

*Essential Oils - Bioactive Compounds, New Perspectives and Applications*

A number of monoterpenes are oxygenated (**Figure 15**).

*3.1.3 Sesquiterpenes*

*3.1.4 Diterpenes*

**3.2 Bioactivities of terpenoids**

disease, malaria, and cancer [34].

medical applications [26].

and insecticides.

skeletons and can be divided into 3 subgroups: acyclic, monocyclic, and bicyclic.

Sesquiterpenes are other major EO components and are less volatile than monoterpenes. They are derived from three isoprene units and exist in a wide variety of forms, including linear, monocyclic, bicyclic, and tricyclic frameworks.

They are chemically complex and are usually components of plants resins but are sometimes encountered as by-products in the isolation of EOs. Diterpenes are less volatile because of their high molecular weights and less numerous than the monoand sesquiterpenes. Consequently, they are difficult to extract by steam distillation and then appear rarely in distilled EOs. When present, they are found in EOs in very low amounts. However, traditional extraction using distillation allows separation and identification of diterpenes present in EOs [136]. Generally, molecules with molecular masses higher than 300 uma can be seen as sign of improper extraction conditions or adulteration. Diterpenes that are usually found in EOs include cam-

Some sesquiterpenoids are very toxic, but some are antifungals, carminatives,

Being complex mixtures of constituents, overall activities of EOs cannot therefore be attributed only to their major components (terpenoids) [137]. Many aroma components of EOs, such as terpenes and terpenoids, were proposed to contribute to their antioxidant activity; that include *β*-terpene and *β*-terpinolene in *Melaleuca alternifolia*, 1,8-cineole in *Mentha aquatic*, and linalool in black cumin. Less volatile but strongly bitter-tasting or toxic terpenes also protect some plant from being eaten by animals. Some terpenes are potent drugs against diseases such as heart

Terpenoids are, by far, the most important group (numerous and structurally diverse) of natural products as far as EOs are concerned. Reports on the level of terpenoids in EOs vary considerably. Many terpenes have biological activities and are used for medical purposes. For example, the antimalarial drug artemisinin and the anticancer drug Taxol (paclitaxel) are two of a few terpenes with established

Monoterpenes are well known as main constituents of EOs, floral, and scents. Monoterpenes and monoterpenoids have antioxidant, anticonvulsant, antiulcer, anti-inflammatory, antiseptic, antitumor, antiviral, analgesic, antihypertensive, antibacterial, and therapeutic antidiabetic properties [26, 138]. The general mechanism of action of monoterpenes, such as their antimicrobial and antitussive activity, is mainly related to their volatility. Their hydrophobicity, as well as the EOs as a whole, determines their effect on bacterial cell structures with a subsequent antimicrobial effect [139]. *α*-Terpineol is used to enhance skin penetration and

Sesquiterpenes are the most diverse group of terpenoids (**Figure 16**).

phorene, cafestol, kahweol, cambrene, and taxideme (**Figure 17**).

**4. Importance of terpenes terpenoids found in essentials oils**

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also has insecticidal properties [140]. Monoterpenes have been shown to exert chemopreventive as well as chemotherapeutic activities in mammary tumor models and thus may represent a new class of therapeutic agents [138]. The EO of *Melissa officinalis* L. can inhibit the replication of HSV-2, due to the presence of citral and citronellal [141]. Linalool is an unsaturated alcohol monoterpene found as principal constituent in many EOs known to exhibit various biological activities that include antibacterial, antiplasmodial, and antinociceptive effects in different animal models [142–144]. Linalool also plays an important role in nature as a key compound in the complex pollination biology of various plant species to ensure reproduction and survival. It is also a key compound for the industrial production of a variety of fragrance chemicals such as geraniol, nerol, citral and its derivatives, as well as a lead compound in the synthesis of vitamins A and E. Its repellent properties on various crop-destroying insects are well studied and documented, hence accentuating the application of linalool in eco-friendly pest management [145]. In Malaysia, linalool is reported to be the major component of EOs of different aromatic species of the Lauraceae family; hence it may be classified as a taxon of this family [146]. Limonene is among the most abundant monoterpene constituents found in nature, and it occurs in a variety of trees and herbs that include *Citrus* species. It has been an interesting target molecule for chemists and biologists. Limonene inhibits LPS-induced NO and PGE2 production that included dose-dependent decreases in the expression of iNOS and COX-2 proteins [147]. Some in vitro and in vivo studies have revealed the effects of monoterpenes on diabetes, insulin resistance, and obesity. The role of inflammation as a link between diabetes and obesity has been established. Many monoterpenes exhibit ameliorative effects in inflammatory conditions associated with diabetes [148]. The analgesic effect of many plant EOs rich in monoterpenes has been established experimentally [149].

Some bicyclic monoterpenoids are known to suppress the acetylcholinesterase activity, which is increased in patient with Alzheimer's disease. In a study of 17 monoterpenes and monoterpenoids, (+)- and (−)-*α*-pinene and (+)-3-carene appeared as potent inhibitors of the enzyme AChE, while the bicyclic ketones and alcohol inhibitions were weak [150].

In recent years, a considerable large number of research studies have been carried out on the chemical constituents of EOs as source of bioactive natural products against cancer. Piaru and collaborators showed that EO of *Myristica fragrans* exhibited good cytotoxic activity, possibly due to the presence of some potential anticancer substances such as limonene, terpinen-4-ol, eugenol, and myristicin [151]. Similarly, EO from *Vepris macrophylla* demonstrated a strong cytotoxic effect, which may be attributed to the presence of specific components like citral, citronellol, and myrcene [152, 153].

Many EO components possess enantiomers that can be sometime present in an oil. It is important to note that there is a close relationship between the chirality of organic compounds and their biological properties. For a given optically active substance, the activity is not identical for both enantiomers [153]. Linalool, for example, has two enantiomers: (3*S*)-(+)-linalool known as coryandrol and (3*R*)-(−)-linalool known as licareol. Both have distinct properties. It was reported that although (*S*)-(+)- and (*R*)-(−)- have similar activity profiles, the effect of (*R*)-(−)-linalool is more intense [154]. Similarly, De Sousa and coworkers showed that regarding the anticonvulsant activity, (*R*)-(−)-linalool and the racemate form were more active than the (*S*)-(+)- enantiomer, which had effects compatible with diazepam and phenytoin, known as anticonvulsant agents [148, 153].

Geraniol, an acyclic aldehyde monoterpene present in various EOs from many aromatic plants, has in vitro and in vivo antitumor activity against several cancer cell lines. In fact, geraniol alters several metabolic pathways of HepG2 cells such

as the mevalonate pathway and the phosphatidylcholine biosynthesis, which results in cell growth inhibition, cell cycle arrest occurring at the G0/G1 interphase, and increased apoptosis [155]. Antibacterial and antifungal activities of oils with high levels of sesquiterpenes as cadinene, spathulenol, and selinene were described [156].

Cristiani and coworkers have reported the antimicrobial activity of four monoterpenes (*p*-cymene, *γ*-terpinene, carvacrol, and thymol) against the Gram-positive bacterium *S. aureus* and the Gram-negative bacterium *E. coli*. They concluded that thymol was considerably more toxic against *S. aureus* than the other three terpenes, while carvacrol and *p*-cymene were the most active against *E. coli* [157]. Germacrene D with its three double bonds as electron-rich centers demonstrated good ability to scavenge superoxide radical anions [156]. However, linalool and nerolidol may also display pro-oxidant activity. Carvacrol and thymol are reported to be the main constituents of volatile oils from *Origanum* species in general [158, 159]. With limonene, citronellol, myrtenol, linalool, and carvacrol are among monoterpenes showing in vitro and in vivo cardiovascular effects in both humans and animals [159].

Monoterpenes, sesquiterpenes, and oxygenated derivatives extracted from EOs have shown strong inhibitory activities against pathogenic bacteria, hence suggesting their use as flavoring and antioxidant agents [104].

Alzheimer's disease is by far the most prevalent of all known forms of dementia. Wojtunik-Kulesza and collaborators showed that three monocyclic monoterpenes (carvone, pulegone, and γ-terpene) possess acetylcholinesterase (AchE) inhibitory activity. Among the investigated terpenes, the three later were recognized as compounds with promising activities in the development of multi-target directed ligands [160]. The lipophilic character of terpene skeleton combined with the hydrophobic character of the functional group is essential for activity. Thus, a rank of activity has been proposed as follows: aldehydes > ketones > alcohols > esters > hydrocarbons [156].

In 2010, Conti and coworkers measured the insect repellent activity of three EOs. They found that at lowest dose (0.001%), the OE of *Hyptis suaveolens* exhibited a significant higher repellent effect compare to *Hyptis spicigera* and *Lavandula angustifolia*. After chemical analyses of the OE of *H. suaveolens*, monoterpene hydrocarbons were the most represented class of volatiles (64.1%), followed by sesquiterpene hydrocarbons (24.0%) [114].

In EOs, the components found in higher concentrations and related to antimicrobial activity are phenolic compounds such as linalool, sabinene, menthol, myrcene, and camphene [161].

Sesquiterpenes have anti-inflammatory and anti-allergic properties. The antiinflammatory activities of some medicinal plants are due to the presence of one or more sesquiterpene lactones [26]. Above all, terpenes are responsible for the smell and flavor typical of the different varieties of *Cannabis sativa*, whereas phytocannabinoids are odorless [162].
