Once structures are identified, we realise further experiments in collaboration with specialised teams to determine their targets and modes of actions and compare their activities with related natural or (semi)-synthetic compounds to assess structure-activity relationships.
We also analysed the possible targets for crude extracts. For example the activity of an extract of Keetia leucantha on different forms of trypanosomas showed a possible effect on glycolysis. We also proved the inhibiting effect of Pterocarpus erinaceus extracts on γ-secretase, an enzymatic complex responsible for A-Beta formation, and the effect of Croton zambesicus or Marrubium vulgare extracts on voltage dependent calcium channels.
Researches on pure isolated compounds allowed us to determine some structure-activity relationships for the vasorelaxant effect of trachylobanes diterpenes (collaboration with N. Morel, IREC). Targets were identified as voltage dependent calcium channels.
Structure-activity relationships for the vasorelaxant activity of trachylobanes
Alkaloids inhibiting topoisomerase I were identified in Cassytha filiformis. Synthetic derivatives were prepared in Spain and were also shown to possess antimalarial properties with a high selectivity index. Structure-activity relationships have been studied.
In the antiparasitic domain, we identified several antitrypanosomal terpenic compounds, some of them inhibiting trypanosomal GAPDH activity, a key enzyme of glycolysis, a process vital for trypanosoma development during its human cycle. We also collaborate with the teams of Prof. J. Palermo (University of Buenos Aires), Profs. J. Poupaert and R. Frédérick (LDRI-CMFA) and Profs. G. Acrombessi and F. Gbaguidi (UAC-Bénin) for the evaluation of the antiparasitic activities of (semi)synthetic compounds and establishment of structure-activity relationships. Some semi-synthetic compounds showed very promising antiplamsodial in vitro activity, in the same range as artemisinin.
The physico-chemical interactions of natural saponins with cholesterol and biological membranes were studied in collaboration with the team of M.P. Mingeot (TFAR-FACM/LDRI) and new results were obtained which could explain several activities of this class of compounds. We also analyse with Prof. Mingeot the interaction of terpenic compounds with parasites membrane models.