Malaria is a life-threatening disease of tropical and subtropical regions, transmitted by female Anopheles mosquitoes and caused by parasites of the genus Plasmodium, with P. falciparum being the most virulent species. The increasing emergence of Plasmodium resistance to currently available antimalarial drugs has significantly reduced the effectiveness of existing therapies, highlighting the urgent need to develop novel antimalarial agents with innovative mechanisms of action.

This project aims to design and synthesize a library of antimalarial compounds based on the β-carboline scaffold, or related heterocyclic systems, hybridized with either (a) artemisinin or (b) chloroquine (CQ), representing an innovative strategy for combating drug-resistant P. falciparum strains. Combining these pharmacophores within a single molecule is expected to produce synergistic effects, improve pharmacokinetic properties, and reduce the likelihood of resistance development.

This interdisciplinary project brings together researchers from different scientific disciplines whose complementary expertise in medicinal chemistry and biological evaluation will enable the successful implementation of the proposed research activities. Advanced computational modelling approaches will complement experimental studies, providing deeper insight into the mechanisms of action of the newly synthesized compounds and enabling the prediction of their biological activities, thereby accelerating the translation from molecular design to potential clinical candidates. The project is expected to identify novel bioactive molecules with the potential to serve as next-generation antimalarial drug candidates, while also contributing to a better understanding of structure–activity relationships (SAR) and to the education and training of young researchers.

Collaboration with researchers from other Croatian and international institutions will contribute to the successful implementation of the project, strengthen scientific networking, and enhance the international visibility of the research group at the University of Zagreb Faculty of Pharmacy and Biochemistry.