INTRODUCTION:

A Steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes which alter membrance fluidity, and as signaling molecules. Hundreds of steroids are found in plants, animals and fungi.

Received on 01.03.2019 Modified on 20.03.2019

Res. J. Pharma. Dosage Forms and Tech.2019; 11(2):126-130.

DOI: 10.5958/0975-4377.2019.00020.X

All steroids are manufactured in cells from the sterols lanosterol (animals and fungi) or cycloartenol. Lanosterol and cycloartenol are derived from the cyclization of the triterpence squalence.

Examples include the lipid cholesterol, the sex hormones estradiol and testosterone and the anti-inflammaiory drug dexamethasone.

These substances constitute the largest group of secondary plant products and show some of the properties of lipids. They are insoluble in water and are derived from the union of a common 5-carbon unit called as isoprene which has a branched carbon skeleton. Isoprene in turn is derived from basic 5-C unit called as isopentane.^[1]

2. Content:

Steroids are Classified as Three Types i.e. Corticosteroids, Estrogens and Progestogens, Androgens. Chemistry of Steroids All steroids have four linked carbon rings, and many of them, like cholesterol, have a short tail. Many steroids also have the –OH functional group, and these steroids are classified as alcohols called sterols. Steroids, such as cholesterol and cortisol, are composed of four fused hydrocarbon rings. Cholesterol is the most common steroid and is mainly synthesized in the liver; it is the precursor to vitamin D. Cholesterol is also a precursor to many important steroid hormones like estrogen, testosterone, and progesterone, which are secreted by the gonads and endocrine glands. These saponins are responsible for the characteristic astringent or bitter taste associated with quinoa To be edible, the saponin must be removed from the quinoa seeds.^[2]

Chemistry of Sapogenins:

Sapogenins are the aglycones, or non-saccharide, portions of the family of natural products known as saponins. Sapogenins contain steroid or other triterpene frameworks as their key organic feature. For example, steroidal sapogenins. Diosgenin and hecogeninare other examples of sapogenins.^[3]

3. Chemistry of Cardiac Glycosides:

A Cardiac Glycosides Therapeutically, this group of compounds may be considered as one of the most important of all natural occurring products. Cardioactive glycosides are steroids having the ability to exert specific powerful action on the cardiac muscle on injection into man or animal.

Lactone rings of the glycosides: The lactone ring of these glycosides is either 5-membered ring i.e cardenolide or 6-membered ring bufadenolide, and these are called either g lactone or d lactone.^[4]

Classification of Terpenes:

Terpenes are classified into many categories based on the no. of carbon atoms and isoprene residues present in their structure:

(i) Monoterpenes -

They consist of 10-C atoms or two isoprene residues.

(ii) Sesquiterpenes –

These contain 15-C atoms or three isoprene residues.

(iii) Diterpenes –

These contain 20-C atoms or four isoprene residues.

(iv) Triterpenes –

These consist of 30-C atoms or six isoprene units.

(v) Tetraterpenes –

These consist of 40-C atoms or eight isoprene residues.

(vi) Polyterpenes –

These consist of large number of isoprene residues.^[5]

4. Stereochemistry of Steroids:

1. The stereo chemistry of the rings markedly affects biological activity of a given class of steroids are six asymmetric carbon atoms 5,8,9,10,13,14 in the nucleus. Therefore 64 optically active forms are possible

2. It can exist in two conformations namely chair form and boat form. • Chair conformation is more stable than boat conformation due to less angle strain. • Hence all cyclohexane rings exist in chair form

3. Hydrogen or functional groups on the β side of the molecule are denoted by solid lines and the α side is denoted by dotted lines.

4. A/B trans • The hydrogen atom at C-5 has α configuration, which is opposite from the c-19 angular methyl group β, making the A/B ring juncture trans

5. Rings B/C and C/D - trans • The configuration of 8 β and 9 α hydrogens and 14 α hydrogen and C-18 angular methyl group denotes trans fusion for rings B/C and C/D. • Cis and trans relationship of the four rings may be expressed in terms of the back bone.

6. 5 α cholestane have trans anti trans anti-trans back bone Anti denotes orientation of ring that are connected to each other and have trans type relationship.

7. 5 β cholestane has Cis –Syn- trans-anti- trans back bone in which the A/B rings are fused Cis. The term Syn is used in a similar fashion as anti to define a Cis type relationship.

8. The number of possible optical isomer is 256. n= 8 • If the chiral centre in the side chain C-20 is also included the number of possible optical isomer will be 512. n= 9 • Two types • Deal with fused rings • Configuration of substituent at C3 and C17

9. In the fully saturated nucleus, there are six chiral centres and hence there will be 64 n=6 optically active forms.

10. It is of worth mentioning that only few exist actually while many cannot exist due to steric limitation. Oxidative degradation method gives a great deal of evidence for the stereo chemistry of the nucleus. In A/B fusion both cis and trans were found in the natural steroids.

11. X-ray analysis reveal that the fusion of the rings B and C was trans. Steroid is a flat which can be explained only if the fusion ring B and C has occurred together in trans manner. Only trans B/C fusion takes place in natural steroid. Ring C/D possestrans fusion.

12. Mostly steroids have trans C/D fusion exception in cardiac glycoside and toad poison in which the fusion is cis. Hydrogen at C-9 is trans to methyl group at C-10.

13. The methyl groups at C-10 and C-13 are Cis • NMR spectroscopy is quite useful in steroid chemistry. • Angular methyl groups undergo coupling with certain protons on the steroid nucleus.

14. It is also found that peak width of angular methyl group half height for trans fused isomer is larger than that for cis fused isomer

15. Configuration of hydroxyl group at C-3 • β series found in all natural steroids. • The prefix β indicates that it lies above the plane of molecule. • If hydroxyl group lies below the plane it gives rise to α series.^[6,7]

5. Structural Elucidation of Drugs Belonging to Mono Citral:

Citral 3,7-dimethyl-2,6-octadienal or lemonal, is either a pair, or a mixture of terpenoids with the molecular formula C₁₀H₁₆O. The two compounds are double bond isomers. The E-isomer is known as geranial or citral A. The Z-isomer is known as neral or citral B.

Lemongrass oil contains 70–80 percent citral, which may be isolated by distillation. Other natural sources include the oils of verbena and citronella. Citral can be synthesized from myrcene. Iononeandmethylionone, made from citral, are used in perfumery; ionone is also converted into syntheticvitamin A.^[8,9]

6. Isolation of Terpenoids:

Three new triterpenoids; namely 28,28,30-trihydroxylupeol; 3,21,21,26-tetrahydroxylanostanoic acid and dehydroxybetulinic acid and seven known compounds; i.e., taraxerone; taraxerol; ethyl palmitate; herniarin; stigmasterol; ursolic acid and acetyl ursolic acid were isolated from the stem of FicusaurantiacaGriff. The structures of the compounds were established by spectroscopic techniques. The compounds were evaluated for their inhibitory effects on polymorphonuclear leukocyte (PMN) chemotaxis by using the Boyden chamber technique and on human whole blood and neutrophil reactive oxygen species (ROS) production by using a luminol-based chemiluminescence assay. Among the compounds tested, compounds 1–4, 6 and 9 exhibited strong inhibition of PMN migration towards the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP).

Characterization of the Isolated Compounds Successive separations of n-hexane, ethyl acetate and methanol extracts using silica gel chromatography afforded three new triterpenoids, 28,28,30-trihydroxylupeol(1), 3,21,21,26- tetrahydroxylanostanoic acid(2) and dehydroxybetulinic acid(3) along with five known triterpenoids, taraxerone(4), taraxerol(5), stigmasterol(8), ursolic acid(9), acetyl ursolic acid(10), one sesquiterpenoid, herniarin(7) and one diterpenoid, ethyl palmitate(6). The structures of the new compounds are shown in Figure 1. The structures of the known compounds were elucidated by the combination of ESIMS, 1H- and 13C-NMR spectral data and comparison of their spectral data with literature values.^[10]

Fig. 1 New terpenoids from F aurantica

7. Isoprene Rule and General Method

Definition of Isoprene - A flammable liquid unsaturated hydrocarbon C₅H₈ used especially in synthetic rule.

Isoprene Rule:

Formally, in biosynthesis of terpenes, two or more isoprene molecules are linked to one another. Linking between two isoprene molecules could occur in three ways, given that the head and the tail of the molecule are primarily involved in the linking:^[11]

1-1 Linkage:

The head of one isoprene molecule could link with the head of another isoprene molecule.

This link is called a head – to – head or 1-1 link

The isoprene rule states that, in most naturally occurring terpenes, there are no 1-1 or 4-4 links.

eg. 1:

Figure 1: Myrcene

8. Chemistry of Contraceptive Agent Male And Female Sex Hormones:

Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method the combined oral contraceptive pill was first marketed as a contraceptive in 1960. In the ensuing decades many other delivery methods have been developed, although the oral and injectable methods are by far the most popular. Altogether, 18% of the world's contraceptive users rely on hormonal methods. Hormonal contraception is highly effective: when taken on the prescribed schedule, users of steroid hormone methods experience pregnancy rates of less than 1% per year. Perfect-use pregnancy rates for most hormonal contraceptives are usually around the 0.3% rate or less. Currently available methods can only be used by women; the development of a male hormonal contraceptive is an active research area. There are two main types of hormonal contraceptive formulations: combined methods which contain both an estrogen and a progestin, and progestogen-only methods which contain only progesterone or one of its synthetic analogues (progestins). Combined methods work by suppressing ovulation and thickening cervicalmucus; while progestogen-only methods reduce the frequency of ovulation, most of them rely more heavily on changes in cervical mucus. The incidence of certain side effects is different for the different formulations: for example, breakthrough bleeding is much more common with progestogen-only methods. Certain serious complications occasionally caused by estrogen-containing contraceptives are not believed to be caused by progestogen-only formulations: deep vein thrombosis is one example of this.

Adrenocorticoids:

CORTISONE:

Cortisone, also known as 17α,21-dihydroxypregn-4-ene-3,11,20-trione, is a pregnane (21-carbon) steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to cortisol. It is used to treat a variety of ailments and can be administered intravenously, orally, intra-articularly (into a joint), or transcutaneously. Cortisone suppresses the immune system, thus reducing inflammation and attendant pain and swelling at the site of the injury. Risks exist, in particular in the long-term use of cortisone.^[12]

9.Contraceptive Agents and Steroids

1. Cardio glycoside Ø SOURCE OF Cardio glycoside ØDigitalis ØVitamin D ØVitamins D3 and D4

2. Cardiac glycosides Plant glycosides with specific action on heart

Historical use: to assasinate people, arrow poisons, Historical sources: South American toad skins, African plant extracts, Modern use:to treat congestive heart failure (dropsy) aglycone structure important for activity

3. Cardio glycoside and other similar glycoside are composed of 2 portions; the sugar moiety, and the non sugarmoietyAglycones. The aglycone portion of the cardiac glycosides is a steroid nucleus with a unique set of fused rings. Ring A-B and C-D are cis fused. whereas B-C have a trans configuration.2 angular methyal groups at C10 and C13. Hydroxyl groups are located at C3, the site of sugar attachment, and C14. C14 hydroxyl is normally unsubstituted. Additional hydroxyl groups may be found at C12 and C-16.

4. The lactone ring at C-17 is another major structure feature of the cardiac glycone. The size and degree of unsaturation of the lactone ring varies with the source of glycoside. The plant glycoside posses a 5- membred, α, β- unsaturated lactone ring. Whereas from animals 6- membered lactone ring with two conjugated double bonds

5. Sugar. The hydroxyl group at C-3 of the aglycone portion usually is conjugated to a monosaccharide or a polysaccharide with β-1, 4-glucoside linkage the most commonly sugar founds in the cardiac glycoside are D- glucose, D-glucose, L-rhamnose, and D- cymarose

6. Sources Scrophulariaceae Digitalis purpurea leaves (foxglove) Digitalis lanata leaves – white flowers Apocyanaceae Strophanthus vine seeds – Africa LiliceaeUrginea bulbs (squill) – Europe, India Convallaria leaves – also produces a volatile oil perfume.

^7.Vitamin D. This vitamin is the anthracitic vitamin; it is essential for bone formation, its function being the control of calcium and phosphorous metabolism. At first it was belived that the precursor of the active compound was Cholesterol, but subsequently the precursor was shown to be some ”impurity”. That was in cholesterol fraction. The ultraviolet absorbance spectrum of this “impure cholesterol” indicated the presence of small amount of some substance that was more unsaturated than cholesterol. this led to suggestion that Ergosterol was the provitamin D in the “impure cholesterol”. ^[13]

CONCLUSION:

Since their discovery, steroids have infiltrated nearly every branch of medicine and can be administered in nearly every route available. The effects of steroid use can vary widely, and the full spectrum of side effects can be present even in patients taking low doses. Practitioners must be aware that the drug can possibly exacerbate a preexisting condition or present a new medical condtion. Knowledge of the clinical implication of prescribing these agents is critical.

A vast number of terpenoids have been evaluated as potential anti-Inflammatory molecules not only in in-vivo animal modles, but also in well defined ex-vivo cultures of cells compromised in the inflammatory response, Such as monocyte/macrophages, neutrophils, mastocytes and leukocytes. In addition to this, some clues coming from the use of plant extracts rich in these terpenoids and administered in traditional medicine, point to the existence of likely candidates to act as potent anti-inflammatory drug.

REFRENCE:

1. William Charles Evan, saunders, “Textbook of pharmacognosy”, 14^th edition, Page No – 293.

2. Dr.K.R. Mahadik and Dr.K.G. Bothara. “Principle of medicinal chemistry” Nirali Prakashan, Volume 2^nd, Page No – 17.1.

3. C.K. Kokate. A. P. Purohit. and S.B. Gokhale. “Textbook of Pharmacognosy”, Nirali Prakashan, 52th, edition, Page No – 1.01.

4. Dr.S.H. Ansari. “Essentials of Pharmacognosy”, Birla Publication, Page No- 251, 207.

5. Papanov G, bozov P, Malakov P (1992) Triterpenoids from lavandula spica. Phytochemistry 31:1424.

6. Applezweig N (1964) Steroid Drug. Volume- 2^nd, Index of Biologically Active Steroids.

7. Evans (1988) “The steroid and thyroid hormone receptor superfamily”, Page No- 889.

8. Orti, et al “Phosphorylation of steroids hormone receptor”, Endor. Rev.13: 105-128

9. James R. Hanson. The development of strategies for terpenoids structure determination, Nat.Pro.Rep., 18, 2001, 607-617.

10. Rassol N, Khan AQ, Malik A (1989) Psoracinol, a new lupine type triterpene from Psoralea plicara. J N Prod52:749

11. Cantrell, C. L.; Franzblau, S. G.; Fischer, N. H. Antimycobacterial Plant Terpenoids.Planta Med.2001, Page no- 685.

12. Wolfang Voelter, some recent aspects in the structure elucidation of natural product, pure and Applied chemistry, 48, 1976 105- 126.

13. Patimoo P. A text BOOK of medicinal Chemistry, CBS Publisher, Ed, 2006, 1

14. Wilson, Gisvold’s Textbook of Organic Medicinal and Phaemacetical Chemistry, Published by wolters Kluwer Pvt.Ltd, Ed, 2012, 6.

15. tps://www.creative-enzymes.com

16. www.biologydiscussion.com

17. www.indianbotanists.com

Received on 30.09.2018 Modified on 18.11.2018

Res. J. Pharma. Dosage Forms and Tech. 2019; 11(2): 121-125.

DOI: 10.5958/0975-4377.2019.00019.3