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Invasive fungal infections are a major cause of morbidity and mortality in immunodeficient individuals (such as AIDS patients) and in transplant recipients or tumor patients undergoing immunosuppressive chemotherapy. Amphotericin B is one of the oldest, yet most efficient antimycotic agents. However, its usefulness is limited due to dose-dependent side-effects, notably nephrotoxicity. In order to improve its safety margin, new pharmaceutical formulations of amphotericin B have been designed especially to reduce its detrimental effects on the kidneys. Since the 1980s, a wide variety of new amphotericin B formulations have been brought forward for clinical testing, many of which were approved and reached market value in the 1990s. This review describes and discusses the molecular genetics, pharmacological, toxicological, and clinical aspects of amphotericin B itself and many of its innovative formulations.

Natural products are not only the basis for traditional or ethnic medicine. Only recently, they have provided highly successful new drugs such as Artemisinin. Furthermore, screening natural products found in all sorts of environments such as the deep sea, rain forests and hot springs, and produced by all sorts of organisms ranging from bacteria, fungi and plants to protozoa, sponges and invertebrates, is a highly competitive field where all of the major pharmaceutical companies are encountered. Already, many new natural product groups have revealed antiparasitic properties of surprising efficacy and selectivity, as will be shown in this review for plant-derived alkaloids, terpenes and phenolics. Many novel lead structures, however, have severe chemico-physical drawbacks such as poor solubility. Here, innovative drug formulations and carrier systems might help, as discussed by the authors in another article of this series.

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