Descripción: The Barcelona Institute for Global Health (ISGlobal) is a cutting-edge institute addressing global public health challenges through research, translation into policy and education.
ISGlobal has a broad portfolio in communicable and non-communicable diseases including environmental and climate determinants, and applies a multidisciplinary scientific approach ranging from the molecular to the population level.
Research is organized in the following main areas: Malaria and other Infectious Diseases, Maternal, Child and Reproductive Health, Urban Health and Child and Environmental Health, Climate Non-Communicable Diseases.
ISGlobal is accredited with the Severo Ochoa distinction, a seal of excellence of the Spanish Science Ministry.Lugar: BarcelonaIntroduction to the vacant position: The Nanomalaria Group is looking for a highly qualified researcher with a synthetic chemistry background and expertise in biological evaluations, particularly in Plasmodium falciparum cultures and the cellular biology of malaria parasites.
The contract will be within the framework of one of the research lines of the Nanomalaria Group, whose objective is the characterization of the inhibition of protein aggregation as a novel mode of action of future antimalarial drugs.The available arsenal of antimalarial drugs is insufficient to progress towards eradication of the disease, a scenario that is worsened by the rampant evolution of resistance by Plasmodium.
This situation calls for immediate efforts to discover new antimalarials of easy and cost-affordable production, having several molecular targets in the pathogen and acting through new antiparasitic mechanisms not shared by currently used drugs.The bis(styrylpyridinium) salt YAT2150 has a number of properties that make it highly interesting as an antimalarial drug, namely: (i) its synthesis is easy and rapid (only two steps), which results in an attractive activity/cost ratio; (ii) its mode of action (inhibition of protein aggregation in the parasite) presumably targets multiple proteins, which would likely prevent rapid resistance evolution; (iii) it belongs to an unexplored chemical family where no other antimalarial has been described to date; (iv) preliminary data suggest that YAT2150 might be active against all Plasmodium species causing human malaria; (v) this molecule fluoresces when interacting with its molecular targets in Plasmodium cells; (vi) it targets all stages of the parasite in the vertebrate host and in the mosquito vector; (vii) the compound has a long shelf life (months) at room temperature; (viii) it has a low parasite in vitro growth half-maximal inhibitory concentration (IC50) below 100 nM.These characteristics place YAT2150 as a highly promising model for a new generation of antimalarial drugs for the post-artemisinin era.
However, the 50% cytotoxic concentration (CC50) of YAT2150 for human cells results in a selectivity index (SI: CC50/IC50) below 100.
The perspectives of a successful clinical development of YAT2150 as an antimalarial drug will improve significantly if the SI can be incremented to values above 100.Main objective of the project: To obtain YAT2150 derivatives with a sufficiently favorable selectivity index to allow this new family of antimalarial drugs to enter the preclinical development pipeline.Specific objectives #J-18808-Ljbffr
