Volume 4, Issue 3, December 2014, Pages 338–346
Includes
articles from two meetings: "Anthelmintics: From Discovery to
Resistance", pp. 218--315, and "Global Challenges for New Drug Discovery
Against Tropical Parasitic Diseases", pp. 316--357
Open Access
Invited Article
Reverse pharmacology for developing an anti-malarial phytomedicine. The example of Argemone mexicana
- Under a Creative Commons license
Highlights
- •
- The conventional drug discovery approach is compared with the reverse pharmacology process.
- •
- Argemone mexicana is used as a case study.
- •
- A reverse pharmacology approach is presented for the treatment of uncomplicated malaria.
- •
- The conventional method led to the identification of 3 alkaloids with antiplasmodial activity.
- •
- The few in vitro tests available for malaria is pointed out as a limiting factor in the search for new drugs.
Abstract
Classical
pharmacology has been the basis for the discovery of new chemical
entities with therapeutic effects for decades. In natural product
research, compounds are generally tested in vivo only after full in vitro characterization. However drug screening using this methodology is expensive, time-consuming and very often inefficient.
Reverse
pharmacology, also called bedside-to-bench, is a research approach
based on the traditional knowledge and relates to reversing the
classical laboratory to clinic pathway to a clinic to laboratory
practice. It is a trans-disciplinary approach focused on traditional
knowledge, experimental observations and clinical experiences. This
paper is an overview of the reverse pharmacology approach applied to the
decoction of Argemone mexicana, used as an antimalarial traditional medicine in Mali. A. mexicana appeared as the most effective traditional medicine for the treatment of uncomplicated falciparum
malaria in Mali, and the clinical efficacy of the decoction was
comparable to artesunate–amodiaquine as previously published. Four
stages of the reverse pharmacology process will be described here with a
special emphasis on the results for stage 4. Briefly, allocryptopine,
protopine and berberine were isolated through bioguided fractionation,
and had their identity confirmed by spectroscopic analysis. The three
alkaloids showed antiparasitic activity in vitro, of which allocryptopine and protopine were selective towards Plasmodiumfalciparum. Furthermore, the amount of the three active alkaloids in the decoction was determined by quantitative NMR, and preliminary in vivo
assays were conducted. On the basis of these results, the reverse
pharmacology approach is discussed and further pharmacokinetic studies
appear to be necessary in order to determine whether these alkaloids can
be considered as phytochemical markers for quality control and
standardization of an improved traditional medicine made with this
plant.
Graphical abstract
Keywords
- Reverse pharmacology;
- Traditional medicine;
- Anti-malarial phytomedicine;
- Argemone mexicana
