Natural Products and Drug Discovery

An Integrated Approach

Subhash C. Mandal, Vivekananda Mandal, Tetsuya Konishi

• Publisher: Elsevier
• Year: 2018
• Print ISBN: 9780081020814
• eBook ISBN: 9780081021040
• Topic: Physical Sciences
• Subtopic: Chemistry
• Index: Chemistry

Natural Products and Drug Discovery: An Integrated Approach provides an applied overview of the field, from traditional medicinal targets, to cutting-edge molecular techniques. Natural products have always been of key importance to drug discovery, but as modern techniques and technologies have allowed researchers to identify, isolate, extract and synthesize their active compounds in new ways, they are once again coming to the forefront of drug discovery.Combining the potential of traditional medicine with the refinement of modern chemical technology, the use of natural products as the basis for drugs can help in the development of more environmentally sound, economical, and effective drug discovery processes. Natural Products & Drug Discovery: An Integrated Approach reflects on the current changes in this field, giving context to the current shift and using supportive case studies to highlight the challenges and successes faced by researchers in integrating traditional medicinal sources with modern chemical technologies. It therefore acts as a useful reference to medicinal chemists, phytochemists, biochemists, pharma R&D professionals, and drug discovery students and researchers.- Reviews the changing role of natural products in drug discovery, integrating traditional knowledge with modern molecular technologies- Highlights the potential future role of natural products in preventative medicine- Supported by real world case studies throughout

Section II

Leads From Natural Products

Outline

Chapter 7. The Role of Natural Products From Plants in the Development of Anticancer Agents

Chapter 8. Plant Drugs in the Treatment of Osteoporosis

Chapter 9. Phytodrugs and Immunomodulators for the Therapy of Leishmaniasis

Chapter 10. Natural Products Targeting Inflammation Processes and Multiple Mediators

Chapter 11. Biologically Functional Compounds From Mushroom-Forming Fungi

Chapter 12. Natural Products in Lifestyle Diseases: In Vitro Screening

Chapter 13. Common Toxic Plants and Their Forensic Significance

Chapter 14. Role of Stress in Diseases and Its Remedial Approach by Herbal and Natural Products in Stress-Related Disease Management: Experimental Studies and Clinical Reports

Chapter 15. Antiinflammatory Medicinal Plants: A Remedy for Most Disease Conditions?

Chapter 7

The Role of Natural Products From Plants in the Development of Anticancer Agents

Danielle Twilley, and Namrita Lall Department of Plant and Soil Sciences, University of Pretoria, Pretoria, South Africa

Abstract

Cancer is one of the major causes of mortality worldwide. In 2012, cancer claimed an estimated 8.2 million lives, while another 5.8 million people were still living with cancer, equating to a total of 14 million cancer cases. The number of cancer cases is predicted to rise by about 70% within the next 20 years, increasing the amount of cancer cases to 24 million by 2035. Natural products remain an important source for the discovery and development of new anticancer drugs. More than 50% of the anticancer drugs are derived from natural products. Plant-derived drugs can be developed as an isolated pure compound or as derivatives and analogs that have been synthesized from the original compound. Plants are one of the important sources for potential anticancer agents due to the ability to synthesize important secondary metabolites. These secondary metabolites are categorized into three different classes—alkaloids, terpenoids, and flavonoids, which provide a source of great structural diversity and thereby a greater variation in biological activity. This chapter summarizes the use of plant-derived drugs for use against various types of cancers as well as an overview of the mechanism of action of flavonoids, terpenoids, and alkaloids. It also discusses the role of plant-derived drugs in current cancer treatments.

Keywords

Alkaloids; Anticancer; Cytotoxicity; Flavonoids; Mechanism of action; Natural products; Terpenoids

1. Introduction

Plants have been used for many years as a source of medicine for the treatment of various diseases. Early medicines from plants were used in the forms of powders, tinctures, teas, poultices, and various other herbal formulations. Plants are important sources for the discovery of new drugs due to their abundance of natural products. Natural products are small molecule secondary metabolites, such as terpenoids, flavonoids, and alkaloids, which are used for the survival of the plant [1]. These secondary metabolites can also be found in various microorganisms such as yeast and bacteria, as well as marine organisms [2,3].

One of the earliest records for using natural products as a source of medicine was found on clay tablets in cuneiform, a system of writing developed by Sumerians in Mesopotamia (2600 BC). The clay tablet depicted the use of Cypress and myrrh oils and more than 1000 plant-derived medicines. The ancient Egyptians were also well known for using plants as a source of medicine. Their pharmaceutical uses of plants were recorded in the Ebers Papyrus (2900 BC), in which more than 700 plant-based medicines were described by using them as ointments, infusions, mouthwashes, and pills [4,5].

It is interesting to note that of the available anticancer drugs currently on the market, 70% have been sourced from natural products or have been derived from plants [3]. It has been reported that approximately 65%–80% of the world's population in developing countries depends primarily on plants for their health care needs [6]. It is further estimated that 35,000–70,000 plant species around the world have been used for their medicinal value, which equates to 14%–28% of the 250,000 plant species found around the world [7].

2. Natural Products and Their Anticancer Activity

In this chapter, the role of different natural products such as terpenoids, flavonoids, and alkaloids for their potential as anticancer agents is discussed. According to a prediction [8], the number of cancer cases is expected to increase by 70% from 14 million cancer cases in 2012 to 23.6 million cancer cases by 2030, so it is important to discover new anticancer drugs and plants provide a great source.

2.1. Terpenoids

Terpenoids make up the largest class of natural products, consisting of approximately 25,000 various chemical structures [9]. Terpenoids can also be referred to as terepenes or isoprenoid, as terpenoids are synthesized from two five-carbon building blocks knows as isoprenoids. The terpenoids further consist of several subclasses: monoterpenoids (C₁₀), diterpenoid (C₂₀), triterpenoids (C₃₀), tetraterpenoids (C₄₀), polytepenoids (C₅)_n, and sesquiterpenoids (C₁₅) [2,3].

2.1.1. Mechanism of Action of Terpenoids

Terpenoids act through a wide network by modulating various regulator factors, signaling pathways, enzymes, and proteins to inhibit the growth, proliferation, invasion, metastasis, and angiogenesis of different types of cancer cells (Table 7.1). Huang et al. [51] and Sobral et al. [52] provide a detailed review of various terpenoids, their anticancer activity, and their mechanism of action. Some of these mechanisms are summarized next.

1. • Apoptosis: Apoptosis can be induced through the extrinsic/death receptor pathway or through the intrinsic...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Foreword
• Preface
• Section I. Traditional Medicine and Drug Discovery
• Section II. Leads From Natural Products
• Section III. Herbal Drug Research
• Author Index
• Subject Index