Terpenoid

Introduction

• In general, terpenoids, may be defined as natural products whose structures are considered to be divided into several isoprene units; therefore, these compounds are invariably termed as isoprenoids.

• Besides, this particular group of compounds is sometimes collectively referred to as the terpenes in relatively older texts.

• Logically, the–oid suffix seems to be more acceptable and convincing, as it is in the same vein for steroids, alkaloids, flavonoids, etc.,

• However, the-ene suffix must be solely confined to the unsaturated hydrocarbon belonging to this specific class of compounds.

Introduction

• Terpenoids are broadly classified on the basis of the number of isoprene units incorporated into a specific unsaturated hydrocarbon terpenoid molecule, such as:

(a) Monoterpenoids: These are built up of two isoprene units and have the molecular formula C10H16;

(b) Sesquiterpenoids: These are composed of three isoprene units and have the molecular formula C15H24;

(c) Diterpenoids: These are comprised of four isoprene units and have the molecular formula C20H32;

(d) Triterpenoids: These contain six isoprene units and have the molecular formula C30H48; and

(e) Tetraterpenoids These are made up of eight isoprene units and have the molecular (or Carotenoids): formula C40H64

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• Biogenetic Isoprene Rule The very idea and basic

concept that terpenoids are essentially built up of several isoprene units is commonly termed as the biogenetic isoprene rule as could be observed from the various typical examples cited earlier.

• Meroterpenoids It has been observed that a good number of other natural products do exist which essentially belong to mixed biosynthetic origin and are mostly made up from isoprene as well as nonisoprenoid entities.

Sesquiterpenoids

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Sesquiterpenoid Lactones

• Sesquiterpenoid Lactones Interestingly, another class of compounds essentially bearing such characteristic features as an α-methylene γ-lactone system; α, β-unsaturated carbonyls, and epoxides and obiviously chemically distinct from the sesquiterpenoids are collectively termed as sesquiterpenoid lactones

Sesquiterpenoid Lactones

• Biological Source It is obtained from the leaves and the closed, unexpanded flower heads of Artemisia annuna Linn., belonging to family Asteraceae

• Uses 1. The drug and its derivatives are used as fast acting blood schizontocides in

the control and management of malarial fever caused by plasmodium vivax strain.

2. These drugs are found to be active against both chloroquine resistant and chloroquine sensitive strains of Plasmodium falciparum.

3. These drugs are found to show extremely encouraging therapeutic effects specifically in the treatment of Cerebral malaria by virtue of their significant rapid clearance of the prevailing parasites when compared to either chloroquine or quinine (synthetic antimalarials)

Sesquiterpenoid Lactones

• Biological Source It is obtained from the leaves of Tanacetum parthenium (L.) Schultz-Bip, (Asteraceae) ; Chrysanthemum parthenium (L.) Bernh. (Compositae);and Magnolia grandiflora (L.) (Magnoliaceae)

• Uses 1. It is found to act as a serotonin antagonist thereby causing an inhibition of

the release of serotonin from blood platelets. 2. Based on the findings conducted by an elaborated double blind placebo-

controlled clinical trials have established that the drug is significantly effective in the prophylaxis of migraine by reducing considerably the severity as well as the frequency of the pain due to headache.

3. A normal dose of 125 mg per day of good quality dried leaves either in the form of tablets or capsules are used in the therapeutic practice as an antipyretic or febrifuge.

Diterpenoids • Generally, diterpenoid represent a broad class of non-

volatile C2O compounds that have been essentially obtained from geranyl pyrophosphate

• It has been observed that they mostly originate from the plant or fungal sources, but they are invariably formed by certain insects as well as marine organisms

Diterpenoids

• Biological Source It is obtained from the root of Coleus forskohlii, Briq., (Labiatae).

• Uses 1. It is used in the purification of adenylate cyclase; and as a result it

serves as a vital research tool in cyclic AMP-related investigations. 2. It also finds enormous use in glaucoma and hypertension. 3. It possesses significant therapeutic potential in diseases like:

congestive cardiomyopathy and bronchial asthma wherein the excessive long term usage of β-adrenergic agonist drugs (e.g.; propranolol, labetalol) ultimately results into the desensitization of the receptors and a loss of drug efficacy.

• Biological Source It is obtained from the root bark and leaves of Ginkgo biloba L., (Ginkgoaceae).

• Uses 1. The standardized dehydrated acetone–water extract of the dried

leaves equivalent to 6% terpenoids and 24% flavone glycosides is sold commercially in Europe as an approved drug to enhance blood fluidity and circulation.

2. In the United States only the tablets containing 40mg of the Ginkgo is allowed to be sold as a ditary suppliment.

3. Ginkgolides A,B, C and M have been shown to suppress the platelet activating factor (PAF) thereby preventing the bronchoconstriction, hypotension, cutaneous vasodilatation and finally the release of inflammatory compounds.

Diterpenoids

• Biological Source It is obtained from the bark of the Pacific Yew tree, Taxus brevifolia Nutt (Taxaceae)

• Uses 1. Taxol is primarily employed in the treatment and management

of metastatic carcinoma of the ovarian glands after the failure of follow-up chemotherapy.

2. It is also used in the treatment of breast cancer usually after the observed failure of combination chemotherapy for metastatic disease.

3. Because of its hydrophobic nature the injectable concentrate of taxol formulation meant for intravenous infusion is normally solubilized duly in polyoxyethylated caster oil. However, before injection it should be appropriately diluted in normal saline or dextrose solution or combination thereof

Diterpenoids

Taxol

Triterpenoid

• Triperpenoids, generally are obtained by biogenesis from six isoprene units, they are found to share commonly the acyclic precursor squalene (C30).

• The triperpenoids may be categorized into two major groups, namely: the tetracyclic and the pentacyclic compounds: the former ones of the steriodal types with C-27 carbon atoms present in the skeleton while the latter are of the triterpenoid types with C-30 carbon atoms as shown below:

Triterpenoid

• Biological Sources Cucurbitacins are obtained primarily from most plants

belonging to the Cucurbitaceae family, namely: Luffa acutangula (Linn.) Roxb. (Ridged or Ribbed gourd); Luffa cylindricaa (Linn.) M. Roem (Luffa aegyptiaca Mill ex Hook f. (Dish-cloth gourd, Vegetables sponge, Spongegourd)], Luffa echinata var longystyla Clarke (supposed to be a hybrid of L. graveolens Roxb. And L. aegyptica Mill); and Luffa graveolens Roxb. It is also found in various species belonging to family viz., Begoniaceae, Cruciferae, Datisceae, Euphorbiaceae, and Scrophulariaceae.

• Uses 1. It has antineoplastic and anti-gibberellin activity. 2. The plants have been employed as vermifuges, narcotics, emetics and

antimalarials. 3. They have also been implicated in sporadic livestock poisoning in South

Africa

• Biological Source It is one of the bitter constituents of the wood of Quassia amara L., (Simaroubaceae), usually known in commerce as Surinam quassia. It is also obtained from the dried wood of Pierasma quassioldes Benn., Picrasma excelsa (Picroena excelsa or Aeschrion excelsa) (Simaroubaceae)

• Uses 1. Its bitterness threshold is found to be 1: 60,000; and hence used as

bitter tonic. 2. It also finds its application as an insecticides and an anthelmintic for

the expulsion of threadworms. 3. It is also used as a febrifuge. 4. Quassin possesses antifertility activity, thereby inhibiting

testosterone secretion of rat Leydig cells

Triterpenoid

• Biological Sources It is obtained from the seeds of Azadirachta indica A. Juss., (Melia ozadirachta L.) and Melia azedarach L., (Meliaceae)

• Uses

1. It is a highly active feeding deterrent and growth regulator.

2. It is used experimentally as insect control agent.

3. It helps in insect ecdysis and growth inhibition**

Triterpenoid

Tetraterpenoids and Carotenoids

• A plethora of natures yellow, orange, red and purple colours are mostly by virtue of the presence of carotenoids.

• The essentially consist of an important group of C40 tetraterpenoids. Invariably, there are two specific regions in a living plant wherein the biogenesis of carotenoids usually occur, namely: chloroplasts and chromatophores of bacteria and fungi

• There are two characteristic features that have been observed in such types of naturally occurring compounds, namely:

(a) Additional isopentenyl moieties (H3C—CH==CH—CH2CH3) could be embeded onto the tetraterpenoid backbone to result into the formation of either C45 or C50 carotenoids, as seen in certain microbes. Example Homocarotenoids, and

(b) Oxidation of C40 carotenoids aften yields such carotenoids that do possess less than 40 carbon atoms, Example Apocarotenoids

Carotenoids

• Interestingly, both in plants and micro-organisms the carotenoids have been observed to serve three major roles, namely: first, as photosynthetic pigments; secondly, as photoprotective agents; and thirdly, as membrane stabilization substances

• In contrast, carotenoids in animals serve as a precursor of vitamin A and other retenoids.

• Besides, they also act not only as cancer preventive agents but also as photoprotective agents.

• Perhaps the protective characteristic features of carotenoids, in general, may be due to the easy accessibility to various singly oxygen atoms and ample free radicals, collectively checking the oxidation damage to cells and catering as antioxidants.

Tetraterpenoids

• It mostly occurs in animals (not in plants) such as: milk fat, fish liver oil. However, the naturally occurring carotenoids are duly converted into Vitamin A by the liver. It is mainly extracted from fish liver oils where it invariably occurs in the esterified form

• Uses 1. It is particularly useful in the proper maintenance of vision,

growth and tissue differentiation. 2. The vitamin is employed mainly as a prophylactic when

there exists an insufficient normal dietary intake 3. It helps in the synthesis of specific glycoproteins.

Vitamin A Derivatives (a) 13-cis Retinoic Acid (Synonym Isotretinoin;

Isotrex; Accutane; Roaccutane).

• Uses

1. It is used in acute recalcitrant cystic acne.

2. It is invariably employed in keratinization disorders of the skin, that are mostly preneoplastic.

Vitamin A Derivatives

(b) All–trans Retinoic Acid (Synonyms Tretinoin; Vitamin A acid)

• Uses

1. It is generally used for the treatment of acne vulgaris by virtue of the fact that it enhances epidermal cell mitosis and epidermal cell turnover.

2. It is used in several formulations like cream, solution and gel meant for tropical applications