https://researchportal.port.ac.uk/portal/files/20192880/STOTEN_D_20_04893R2_COVID_19_accepted_article.pdf

COVID-19: A promising cure for the global panic.

Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.

The IUPHAR/BPS Guide to PHARMACOLOGY (www.guidetopharmacology.org) is an open-access, expert-curated database of molecular interactions between ligands and their targets. We describe significant updates made over the seven releases during the last two years. The database is notably enhanced through the continued linking of relevant pharmacology with key immunological data types as part of the IUPHAR Guide to IMMUNOPHARMACOLOGY (www.guidetoimmunopharmacology.org) and by a major new extension, the IUPHAR/MMV Guide to Malaria PHARMACOLOGY (www.guidetomalariapharmacology.org). The latter has been constructed in partnership with the Medicines for Malaria Venture, an organization dedicated to identifying, developing and delivering new antimalarial therapies that are both effective and affordable. This is in response to the global challenge of over 200 million cases of malaria and 400 000 deaths worldwide, with the majority in the WHO Africa Region. It provides new pharmacological content, including molecular targets in the malaria parasite, interaction data for ligands with antimalarial activity, and establishes curation of data from screening assays, used routinely in antimalarial drug discovery, against the whole organism. A dedicated portal has been developed to provide quick and focused access to these new data.

/pdf/the-iuphar-bps-guide-to-pharmacology-in-2020-extending-432aulpxe7.pdf

The IUPHAR/BPS Guide to PHARMACOLOGY in 2020: extending immunopharmacology content and introducing the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY.

Triple Artemisinin-Based Combination Therapies for Malaria – A New Paradigm?

Traditional remedies have been used for thousand years for the prevention and treatment of infectious diseases, particularly in developing countries. Of growing interest, the plant Artemisia annua, known for its malarial properties, has been studied for its numerous biological activities including metabolic, anti-tumor, anti-microbial and immunomodulatory properties. Artemisia annua is very rich in secondary metabolites such as monoterpenes, sesquiterpenes and phenolic compounds, of which the biological properties have been extensively studied. The purpose of this review is to gather and describe the data concerning the main chemical components produced by Artemisia annua and to describe the state of the art about the biological activities reported for this plant and its compounds beyond malaria.

https://hal.univ-reunion.fr/hal-02918790/document

Artemisia annua, a Traditional Plant Brought to Light

Great progress has been made in recent years to reduce the high level of suffering caused by malaria worldwide. Notably, the use of insecticide-treated mosquito nets for malaria prevention and the use of artemisinin-based combination therapy (ACT) for malaria treatment have made a significant impact. Nevertheless, the development of resistance to the past and present anti-malarial drugs highlights the need for continued research to stay one step ahead. New drugs are needed, particularly those with new mechanisms of action. Here the range of anti-malarial medicines developed over the years are reviewed, beginning with the discovery of quinine in the early 1800s, through to modern day ACT and the recently-approved tafenoquine. A number of new potential anti-malarial drugs currently in development are outlined, along with a description of the hit to lead campaign from which it originated. Finally, promising novel mechanisms of action for these and future anti-malarial medicines are outlined.

/pdf/the-past-present-and-future-of-anti-malarial-medicines-l3ax950l1f.pdf

The past, present and future of anti-malarial medicines

We have discovered and studied a tele-substitution reaction in a biologically important heterocyclic ring system. Conditions that favor the tele-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base or the use of softer nucleophiles, less polar solvents, and larger halogens on the electrophile. Using results from X-ray crystallographic and isotope labeling experiments, a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the in vivo active antiplasmodium compounds of Series 4 of the Open Source Malaria consortium.

tele-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials.

We
have discovered and studied a telesubstitution reaction in a
biologically important heterocyclic ring system. Conditions that favour
the tele-substitution pathway were identified: the use of increased
equivalents of the nucleophile or decreased equivalents of base, or the use of
softer nucleophiles, less polar solvents and larger halogens on the
electrophile. Using results from X-ray crystallography and isotope labelling
experiments a mechanism for this unusual transformation is proposed. We focused
on this triazolopyrazine as it is the core structure of the in
vivo active anti-plasmodium compounds of Series 4 of the Open Source
Malaria consortium.

 

Archive
of the electronic laboratory notebook with the description of all conducted
experiments and raw NMR data could be accessed via following link https://ses.library.usyd.edu.au/handle/2123/21890 .
For navigation between entries of laboratory notebook please use file
"Strings for compounds in the article.pdf" that works as a reference
between article codes and notebook codes, also this file contain SMILES for
these compounds.

/pdf/tele-substitution-reactions-in-the-synthesis-of-a-promising-23sblefj7j.pdf

Marat Korsik

Papers

The past, present and future of anti-malarial medicines

tele-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials.

Tele-Substitution Reactions in the Synthesis of a Promising Class of Antimalarials