Natural Products in Clinical Trials

Schistosomiasis, caused by trematode flatworms of the genus Schistosoma, is one of the most significant neglected tropical diseases in about 70 tropical and subtropical countries. It is estimated that over 200 million people are infected and more than 770 million are at risk of infection. S. mansoni, S. haematobium and S. japonicum are the major etiological agents of human schistosomiasis, whose treatment is dependent on a single drug, praziquantel (PZQ). In the light of the exclusive dependency on PZQ, there is an urgent and unmet need to discover novel therapeutic agents against this pathogen. In this chapter, we comprehensively addressed chemical and pharmacological aspects of the schistosomicidal patented compounds in the early 20th century, beginning with antimonials as the first compounds in the schistosomiasis treatment, passing over the next years with many chemical derivatives, such as imidazoline, acridone and carbazoles, and, after, with PZQ and artemisinin, in the 1980s. Also, recent patents have been described covering other drugs, such as Nphosphorylate amino acids, peroxide derivatives, and cysteine protease inhibitors along with new patents based on natural compounds, such as alkaloids, terpenes, and anthraquinones.

Nature is considered an indispensable source of natural products and natural products-derived drug leads. Over the last decade, the use of natural products-based medicine (herbal medicine or phytomedicine) has increased tremendously worldwide especially with the exceeding prevalence of metabolic disorders. Metabolic disorders are the major worldwide epidemic associated with obesity, diabetes mellitus, cardiovascular diseases associated with hyperlipidemia, and many other endocrine and nutrition-related issues. Since metabolic disorders are multi-factorial in their pathophysiology, they can be targeted by natural products that have synergy between diverse metabolites. Therefore, it is important to find the proper formulas not only for the treatment but also for reduction of associated risks and for prophylaxis and prevention of long-term complications. At the present work, a brief outline of the pathophysiology of metabolic disorders is provided. Additionally, natural productbased drug therapies that are currently applied in clinical trials attributed to metabolicrelated diseases are critically discussed.

The incorporation of covalent fluorine has been widely used as an effective strategy in medicinal chemistry for drug discovery. The introduction of fluorine into a molecule can significantly influence conformation, lipophilicity, pKa, metabolism, and pharmacokinetic properties. In 1955, the first fluorinated drug fludrocortisone has been approved in the market for the treatment of the adrenogenital syndrome, postural hypotension, and adrenal insufficiency. Since then, 218 small-molecule drugs with at least one fluorine atom have been launched by U.S. FDA by the end of 2018. Therefore, this chapter is expected to summarize the fluorine-containing natural products in clinical development to the medicinal chemistry community.

Cardiovascular diseases constitute a serious public health problem. It is estimated that they are responsible for nearly 30% of world mortality. Regardless of the developments in the diagnosis and management of cardiovascular diseases, their incidence rate remains increasing. Therefore, newlines of drugs are needed to manage the expanding population of patients with cardiovascular diseases. Even though the most common existing treatments for cardiovascular diseases are synthetic molecules, natural compounds, of different chemical classes, are also being tested. Medicinal plants have been employed in the treatment of some cardiovascular diseases such as congestive heart failure and hypertension many centuries ago. Recently, the traditional remedies application for the treatment of different disorders is gaining revived popularity. In this chapter, we will investigate the efficacy and safety of natural products under preclinical studies and clinical trials with particular emphasis on their traditional uses and implementations in the primary health care system. The great potential of medicinal plants and herbs will be discussed in light of the rising prevalence of cardiovascular diseases as one of the most devastating global health problems.

Our eyes are a window to this world and like other parts of our body are affected by various diseases and injuries. Prevalence of various ocular diseases is although very high, very few remedies are available. Diseases affecting eye and vision are on the rise particularly those associated with potentially blinding conditions such as diabetic retinopathy, age-related macular degeneration, and glaucoma. Prevention appears to be a better modality for most of the ocular diseases compared to that of the treatment options. Natural compounds have found its use in the prevention and treatment of many ocular diseases. Several natural compounds with properties such as anti-oxidative, anti-proliferative, immunomodulatory have been implicated in the prevention of various ocular diseases. However, there are many avenues left for the application of natural compounds for the prevention and treatment of various ocular diseases. Understanding of the probable mechanism responsible for the disease formation, identification of targets, evaluation of candidate molecules by in silico, in vitro and in vivo assays can strengthen the application of natural compounds for the prevention of ocular diseases. Besides disease prevention, natural compounds have also found its use in various ocular surgical procedures.