Anti-obesity Agents: A Focused Review on the Structural Classification of Therapeutic Entities

Abstract

In addition to its enormous impacts on an individual's quality of life, obesity is a daunting health problem in the world today and the increasing rate of obesity is now causing a severe burden on health care systems. Fortunately, the normalization or reduction of increased body fat reverses the obesity-associated morbidities, such as hypertension, glucose intolerance, dyslipidemia, and fatty liver diseases. However, the modification of lifestyle in a case of established clinical obesity is very difficult to achieve. Recent breakthroughs in relation to the molecular mechanism regulating body weight and energy metabolism give us hopes for the development of anti-obesity drugs. Even with the high social demand for an effective treatment for obesity and extensive researches, both in academia and the pharmaceutical industry, only two weight-loss drugs, sibutramine and orlistat, have been approved by the FDA for long-term treatment. In addition, the current bottleneck in drug discovery shows that a more detailed understanding of the pathogenesis of obesity is an essential element for the development of efficacious treatment. In this review article, we focus on the structural origin of chemical entities for anti-obesity treatment along with the rationale for drug discovery, rather than categorizing the clinical efficacy or pharmacological target of obesity. For the clarification of the structural origin, we formed a collection with 4 major groups, including natural products, natural product mimetics, synthetic small molecules, and peptides/hormones. This analysis might provide strategic plans for medicinal chemists, biologists, and physicians to begin an optimistic era with a new class of pharmaceutical adjuncts for obesity therapy.

Approved and Off-Label Uses of Obesity Medications, and Potential New Pharmacologic Treatment Options

“…Effective treatment of obesity will probably require a combination of drugs acting at different points in this complex system. A review focused on the structural classification of the anti-obesity agents has recently been published [15]. …”

Natural Product-Based Drug Discovery

“…An ethanolic extract of Morus alba leaves has shown anti-obesity effects in diet-induced obese mice [178], while black and green teas have exhibited effects against the metabolic syndrome and cardiovascular disease in rat models of human obesity [179]. The selective elevation of adiponectin production by astragaloside II and isoastragaloside I has raised hopes in this respect [180].…”

Induction of NAFLD with Increased Risk of Obesity and Chronic Diseases in Developed Countries

“…Various anti-obesity drugs that target the CNS and peripheral tissues such as the adipose tissue, liver and muscle have shown promise over the past 100 years however withdrawal of these drugs recently [157]- [159] has resulted in the avoidance of harmful side effects to various obese individuals. The discovery of novel CNS compounds that are in the early phase and are under clinical development allows for assessment of agents that allow weight reduction with alteration in serious medical complications of obesity [160]- [164]. Figure 2.…”