Steroids and their Medicinal Potential

Terpenes belong to the largest class of secondary metabolites consisting of five carbon isoprene units which are assembled through innumerable patterns generating diverse structural motifs. Terpenes are linear or cyclic hydrocarbons, whereas terpenoids are oxygen-containing terpene analogues found in all living organisms. Steroids are a subclass of terpenoids that are biosynthesized from terpene precursors. Terpenes, terpenoids and steroids are all derived from five-carbon isoprene units assembled and arranged in different ways generating thousands of structurally varied molecules. Terpenes and terpenoids are widely explored as biomaterials and biofuels while steroids are used as drugs to increase protein synthesis in animals besides their anti-inflammatory, anticancer and other properties. In this chapter, we discuss the properties, functions and biosynthesis of terpenes and terpenoids in general and steroids in particular to better understand their functions and prospective applications.

Natural steroids are organic compounds that play important physiological roles in various organisms. They are the key components of a cell, which act as important signalling molecules engaging in stress response, metabolic activities, reproduction, inflammation, and behavioural uniformities. Naturally, the human body embraces a cluster of steroids in the form of biological hormones, namely, sex hormones, adrenal cortical hormones and bile acids. Steroidal derivatives can imitate human hormones and exhibit their activities by boosting enzymes that the body lacks. Clinically, it is evident that the distribution of synthetic steroids is high in pharmaceutical use for hormonal anomalies, but they provide adverse side effects over long term usage. Steroids work as immunosuppressants to control many autoimmune disorders concerned with inflammation, but they also reduce the activity of the immune system, which is the body’s natural defence against infection and illness. Replacement of natural steroids sourced from herbal plants, marine invertebrates, bacteria, algae, and fungi has a medicinal value that aids in the treatment of various ailments. Apart from hormonal functions, bio-derived steroids also display a safe and copious pharmacological profile for anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-neoplastic, neuroprotective, and cardioprotective activities. This chapter discusses the prevalence of various naturally available steroids in different entities and their suitable applications in various fields.

 The term steroid pertains to a broad spectrum of molecules with varying physiological roles. More explicitly, they are a class of compounds that are naturally produced in the body of living organisms as well synthetic or semi-synthetic molecules. They have tremendous effects on biochemical processes and thus any aberration from the required physiological range can have potential effects. Moreover, due to the therapeutic potential of steroids for the treatment of a wide range of diseases, many synthetic approaches have been made available to the organic chemist for their synthesis. Most of the steroids that are in use as drugs are still prepared by modifying naturally occurring steroids (partial synthesis). This chapter highlights the biosynthetic pathways of steroids and the approaches to chemically synthesize them because of their biological and synthetic relevance. 

Natural products account for 60% of the total market, making them a major source of drug discovery. Some of these are sourced from the cultivation of microorganisms. Microbial transformation is an example of the application of the cultivation of microorganisms. It is a method of modifying the chemical structure of compounds such as steroids by microorganisms. The diversity of the possible reaction types in microbial transformation includes the process of oxidation, hydroxylation, esterification, isomerization, reduction, acetylation, hydrogenation and glycosylation. Therefore, screening of new microbial strains for specific bioconversions is essential for bioprospecting. This chapter reviews a range of previous studies that have used fungi for biotransformation. 

Steroids display varied biological functions and play a crucial role in the fascinating fields of biology, chemistry, and medicine.Steroids encompass wideranging natural products which are abundantly encountered in eukaryotic organisms. These exhibit a pivotal role in regulating the cellular functions of animals, plants, and fungi. Furthermore, they act as chemical messengers in the human body and get secreted in the systemic circulation and extracellular fluids, where they regulate metabolic, immune, and reproductive functions. Steroids are the fundamental components of cell membranes and serve primarily as signalling molecules. This chapter gives a comprehensive overview of physiologically active steroids in various organisms.The biological activities of various steroid classes have been discussed in detail. Glucocorticoids are a class of steroid hormones that regulate the metabolic processes involving the formation of glucose from amino acids and fatty acid deposition of glycogen in the liver. Another important group of hormones, called mineralocorticoids, helps in balancing water and electrolyte content in the body and primarily affects the kidney. The principal class of steroids viz. the sex hormones are essentially crucial for the development and maintenance of reproductive function and cause stimulation of secondary sexual characteristics in humans. To summarize, steroids stabilize and regulate the structure and functions of cellular membranes and play a crucial role in regulating growth and development. 

Estrogens (estrone, estriol, and estradiol) are a class of steroidal hormones produced by developing ovarian follicles. These hormones induce various cyclic events in the uterine endothelium and vaginal epithelium and make the female body competent for conception and ultimately for motherly care. While estrogen is primarily produced by ovaries from cholesterol, the non-reproductive tissues including the brain, liver, and heart also produce a considerable amount of it. Apart from its important role in controlling sexual behavior and reproductive function, estrogen also functions in the regulation of various physiological functions including reproduction, skin physiology, cardiovascular health, skeletal homeostasis, bone integrity, electrolyte balance, cognition, and behavior. These biological functions are regulated by diffusion through the plasma membrane in vitro signaling through specific binding to nuclear receptors such as estrogen receptors (ERα and ERβ) or binding to cell membrane receptors such as GPR30 and ER-X. The signaling mechanism can be genomic (change in gene expression) or non-genomic (activation of various signaling cascades). Disruption in estrogen functioning has a pivotal role in the pathogenesis of many diseases such as osteoporosis, insulin resistance, neurodegenerative disease, obesity, and endometriosis. Also, dysregulation in the levels of estrogen has been linked to the development of many cancers such as breast cancer, etc. This chapter aims to summarize the complete insight of estrogen by providing a clear understanding of its synthesis, receptor binding, signaling, regulation of physiological functions, and role in various diseases.

Cardenolides are a class of compounds steroidal in nature, belonging to the cardiac glycoside group of secondary metabolites. They consist of a sugar part and a non-sugar part consisting of a steroidal cyclopentanoperhydrophenanthrene ring with lactone substitution at the β-17 position. Cardenolides are found in angiosperm plant families like Plantiginaceae, Asclepiadaceae, Apocynaceae, Brassicaceae, Cruciferae, Liliaceae, Moraceae, Ranunculaceae, and Scrophulariaceae. These include some important glycosides, such as digitoxin, digoxin, Ouabain, Calotropin, etc. with profound pharmacological potential. Moreover, cardenolides have toxic effects for which these have been used in poison arrows and for self-harm purposes. Traditionally, these were used to treat congestive heart failure. However, recently they have emerged as promising agents to exhibit anticancer, antiviral, anti-inflammatory, neuroprotective, and various other therapeutic roles. Cardenolides like Digoxin and Digitoxin have been used in the treatment of heart failure and atrial fibrillation. Toxicarioside A, and Calotropin have been reported to suppress tumor growth and are used as anticancer agents, Strophalloside and Oubain are reported to be involved in apoptosis. Oleandrin is an antiproliferative agent and can inhibit IL-8 which is responsible for cystic fibrosis.

This book chapter compiles a general idea of steroids and their overall biological significance in immunity and immune-associated diseases. Steroids chemically comprise a group of cyclical organic compounds constituted by seventeen carbon atoms that consist of four fused rings called sterane, and cyclopentanoperhydrophenanthrene. The four-ringed structures are mainly synthesized by mitochondria and smooth endoplasmic reticulum through the cyclization of thirty-carbon chain squalene into lanosterol or cycloartenol. Steroid hormones differ only in number of oxygen and carbon atoms, but all are derived from cholesterol. The biological significance of steroids and their derivatives range from energy metabolism, and body growth to the control of reproductive activities. However, deficiency or malfunctioning of steroids can lead to direct effects on body salt/sugar levels, sexual differentiation and immunity. As far as immune responses are concerned, a lot of research works have emerged which show the importance of steroids in immune regulation, and in extreme cases, they are also known to result in immune-related diseases. Most of these effects are mediated by the influence of steroids on gene expression in cells and this could in turn prove to be novel drug targets as well. We have made an attempt in this chapter to update and highlight the role of steroids in immune regulation and immune-related diseases, which we hope would open up therapeutic options for diseases.

Steroids are organic compounds with four rings arranged in a precise molecular configuration and are involved in many biological functions displaying a wide spectrum of biological activities and diverse chemical reactivities. Structural modifications of the steroidal rings have attracted a considerable amount of attention recently. Steroids of natural origin have been modified in several ways, particularly in the cyclopentanophenanthrene ring system with heteroatoms such as nitrogen, oxygen, and/or sulfur or with the heterocyclic ring to obtain more active compounds with less or no harmful side effects and are termed as heterosteroids or heterocyclic steroids. Heterocyclic steroids are enticing as the minor modifications to the steroidal molecules, produce remarkable differences in their biological activities. The introduction of the heteroatom in the skeleton of a steroidal molecule often poses challenges to organic chemists, demanding the exploration of new synthetic reactions and new synthetic routes. In this article, the overview of the various synthetic strategies employed to synthesize azasteroids, oxasteroids, thiasteroids, and steroids modified by the introduction of the heterocyclic ring is broadly covered along with its biological significance. 

All the steroids are basically made of seventeen carbon atom skeletons bonded in four fused rings: three six-membered cyclohexane rings and one fivemembered cyclopentane ring, they vary from each other by having different functional groups. Recent modifications have added heteroatoms like nitrogen, oxygen, sulphur, selenium, etc in the basic structure of naturally occurring steroids. Heterocyclic steroids have always been a field of interest for researchers due to their diverse biological performances. The biological activity of steroids and heterocyclic steroids is based on the structure they possess. Spectroscopy plays a key role in the determination of distinct properties of numerous compounds by their interaction with electromagnetic radiation and the sort of interactions that may occur in different regions. The structure of different steroids and heterocyclic steroids may be established through various spectroscopic techniques viz. Infrared spectroscopy (IR), Nuclear Magnetic Spectroscopy (NMR), Ultraviolet spectroscopy (UV) and mass spectrometry (MS). 

Steroidal drugs are synthetic in nature that are closely identical to naturally produced hormones in our body such as cortisol and testosterone. They are lifesavers for several threatening medical conditions. They are currently in wide use for the treatment of various inflammatory diseases since they are known to involve in suppressing the immune system resulting in a reduced inflammatory process. They are produced in different forms and do not cause any major side effects when consumed at low doses. However, occasionally they lead to perilous side effects when taken in appropriate doses that lead to mental health problems, high blood pressure, diabetes, osteoporosis, etc. Practices such as the uptake of illicit anabolic steroids and corticosteroid drugs without an appropriate prescription can potentially lead to fatal side effects. Anabolic steroids are performance and image-enhancing drugs that were once viewed as predicament associated with bodybuilders and have now become a widespread problem throughout our society including children. Dietary supplements which act as steroidal precursors also promote medical consequences that are similar to steroids and the absence of such awareness in our society leads to varied difficulties in our current lifestyle. The increasing concern about possible health hazards in association with abusive steroid drug uptake should be addressed with strict measures. It is important to educate our society about the hazardous effects of steroidal drug abuse and the precautions that need to be carried out while using them. This chapter highlights different types of steroid drugs that are currently in use and the deleterious side effects caused by their abusive use. Potential treatments for their withdrawal and preventive measures will also be addressed in detail.