Volume 44, 2015, Pages 33–92
Chapter 2 – From Bench to Bedside: Natural Products and Analogs for the Treatment of Neglected Tropical Diseases (NTDs)
Abstract
Parasitic
diseases are a major cause of mortality in many tropical countries,
affecting hundreds of millions people, mostly associated with poor
socioeconomic and hygienic environment. Diseases caused by species of
the genera Trypanosoma (Human African Trypanosomiasis and Chagas disease), Plasmodium species (malaria), and Leishmania
(various forms of leishmaniasis) are among the 17 “neglected tropical
diseases” (NTDs) defined as such by the World Health Organization, due
to the lack of enough financial investment into research and development
of new drugs by most of the pharmaceutical industry and neglect of
public awareness in high-income countries. Existing therapies suffer
from various deficiencies, namely, high degree of toxicity and unwanted
effects, limited availability and affordability, and/or problematic
application under the life conditions of affected populations.
Development of new, safe, and affordable drugs is therefore an urgent
need. Many well-known drugs listed in the modern pharmacopoeia have
their origins in nature, including, for example, quinine from the bark
of the Cinchona tree for the treatment of malaria, which has
been followed by the subsequent development of the synthetic derivatives
chloroquine, amodiaquine, primaquine, and mefloquine. Similarly, the
potent antimalarial activity of artemisinin from the herb Artemisia annua is currently used as an alternative to chloroquinine in China against resistant strains of Plasmodium
and also investigated in the United States by the military forces,
since malaria can quickly debilitate troops. Besides, artemisinin has
led current research to focus on the development of a large number of
synthetic and semisynthetic compounds, which are more active than
artemisinin. In this regard, our research group has been working on
chalcones derivatives as inhibitors of Mycobacterium tuberculosis (tuberculosis), Trypanosoma cruzi, and Leishmania
spp., with some patents been issued [Brazil PI 0204079-4 (2004)]
because of the positive effects found for the treatment of those NTDs.
In this chapter, a comprehensive list of medicinal plants, marine
organisms, and other natural products that have shown activity against
the etiologic agents and vectors/hosts (mainly to dengue and
shistosomiasis) of NTDs is provided. Also emphasis on recent
developments in groups of medicinally important natural products,
particularly with reference to the structure–activity studies, will be
given.
Keywords
- Natural products;
- Chalcones;
- Neglected tropical diseases;
- American trypanosomiasis;
- Molecular modeling
Copyright © 2015 Elsevier B.V. All rights reserved.
