Background: Malaria, caused by the deadly Plasmodium falciparum strain, claims the
lives of millions of people annually. The emergence of drug-resistant strains of P. falciparum to
the artemisinin-based combination therapy (ACT), the last line of defense against malaria, is worrisome
and urges for the development of new chemo-types with a new mode of actions. In the
search of new antimalarial agents, hybrids of triazoles and other known antimalarial drugs have
been reported to possess better activity than either of the parent compounds administered individually.
Despite their better activity, no hybrid antimalarial drugs have been developed so far.
Objective: In the hope of developing new antimalarial prototypes, we propose the design, synthesis
and antimalarial evaluation of novel sulfoximine-triazole hybrids owing to their interesting biological
and physiological properties.
Method: The sulfoximine part of the hybrid will be synthesized via imidation of the corresponding
sulfoxide. Propargylation of the NH moiety of the sulfoximine followed by copper-catalyzed click
chemistry with benzyl azide was envisaged to provide the target sulfoximine-triazole hybrids.
Results: Five novel sulfoximine-triazole hybrids possessing various substituents on the sulfoximine
moiety have been successfully synthesized and evaluated for their antiplasmodial and cytotoxicity activities.
The results revealed that the co-presence of the sulfoximine and triazole moieties along with a
lipophilic alkyl substituent on the sulfur atom impart significant activity.
Conclusion: Sulfoximine-triazole hybrids could be used as a prototype for the synthesis of new derivatives
with better antiplasmodial activities.