Background: Malaria is a serious parasitic infection with greater morbidity and motility
in recent decades. Cysteine protease and DHODH enzyme serve as a potential target for antimalarial
agents which inhibit parasite multiplication in the erythrocyte stage. Development of new leads
which specifically target cysteine protease and DHODH enzyme can reduce the side effects and
overcome multidrug resistance.
Objectives: Representing the design and development of antimalarial agents by targeting cysteine
protease and DHODH (Dihydroorotate dehydrogenase) enzyme by structure-based drug design.
Methods: In present work, the rational development of antimalarial agents by targeting cysteine
protease and DHODH has been made by integrating binding confirmation from virtual analysis and
Results: A novel series of dihydroisoquinolines was designed by structure-based drug design.
Compounds from the dataset were screened for interaction at the target site by performing molecular
docking study and subsequently, all molecules were screened for drug-like properties and toxicity,
prior to synthesis molecules subjected to virtual filters. Designed molecules which exceed these
virtual filters were synthesized, characterized and finally screened for antimalarial activity.
Conclusion: In this work, it has been observed that compound A1, A5, A6 and A9 showed desirable
biological activity towards targets and also specific hydrogen bonding interaction with the targets.
Further optimization in leads yields a drug-like candidate and may overcome multidrug resistance.