Natural products for the control of malariaMalar J. 2011 Mar 15;10 Suppl 1:S1
II. How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?Guantai E, Chibale K
Malar J. 2011 Mar 15;10 Suppl 1:S2
PubMed Central PMCID: PMC3059460
Eric Guantai and Kelly Chibale of the University of Cape Town begin by noting that “other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years”:
“Unfortunately the current reality is that other than compounds that have their foundation in historic natural products (such as quinine, artemisinin, hydroxynaphthoquinones, doxycyclin, clindamycin, and azithromycin), there are no other compounds in preclinical development or further that have originated from a natural product start-point in recent years. There are not even any compounds in current anti-malarial lead optimization projects that have come from natural products in recent years. Many natural products have shown potent anti-plasmodial effects but, for a variety of reasons, including chemical tractability issues, these have not been pushed forward into hit-to-lead drug discovery projects.”
Guantai and Chibale then review several approaches from outside the field of malaria that “could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds,” including: drug combinations; dual drugs/drug hybrids; metabolism and metabolite identification studies; molecular modeling and docking tools; natural product-derived pharmacophores (group of atoms in the molecule responsible for the drug’s action) and template-based virtual screening; natural product databases; and target-identification and reverse pharmacology.
Citing evidence from these approaches of “the potential of natural products to provide or inspire the development of anti-malarial lead compounds,” the authors recommend collaboration across diverse scientific disciplines in the search for novel agents for development:
“The potential of natural products to provide or inspire the development of anti-malarial lead compounds is, therefore, really quite evident. However, to raise the chances of the actual realization of this potential, it has become necessary to think beyond the confines of conventional natural-product drug discovery. The application of a wide variety of scientific tools and the close and interactive collaboration of experts in diverse scientific disciplines (such as chemistry, pharmacology, molecular biology and genetics) has become practically obligatory if these truly multi-disciplinary efforts are to indeed be successful. The fact that literature on the application of some of these approaches towards anti-malarial drug discovery based on natural products is sparse is indicative of their underutilization in this regard, a situation that should arguably be addressed.”
Read the complete article at PubMed Central.
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