Synthesis and evaluation of new marinoquinolines with potential antimalarial activity

Abstract

Protozoa are responsible for most of the parasitic infections that affect humans, especially malaria, which is present in all tropical and subtropical regions of the world. The WHO estimates that 214 million of new malaria cases occurred around worldwide in 2015, with an estimated 438,000 deaths making malaria among the top three infectious diseases. Despite the fact that treatments with quinine and its many derivatives are of primary importance in the control of malaria, resistance and tolerance associated with antimalarial drugs currently available have generated an intense search for new chemical entities with new modes of action. In addition, these new entities should be readily available and to meet the requirements put forward by "Medicines for Malaria Venture (MMV)" for the next generation of drugs needed to eradicate malaria. Thus, with the pharmacological potential of marinoquinolines, the objective of this project is the synthesis of several new derivatives of aplidiopsamine A and marinoquinolines, which composed two promising families of compounds with potential as new chemical entities against P. falciparum. It will be introduced, in a hybrid manner, structural patterns of drugs known as effective and established antimalarial agents, using as key steps the Suzuki-Miyuara or Heck-Matsuda and the Pictet-Spengler reactions, in order to obtain effective derivatives from the point of view of medicinal chemistry. The synthesized compounds will be evaluated for their antimalarial activities by collaborators within the CIBFar / CEPID, to which the research group of prof. Carlos Correia is associated.