The design, synthesis and antiplasmodial evaluation of novel sulfoximine-isoxazole hybrids as potential antimalarial agents

Abstract

A library of novel sulfoximine-isoxazole hybrids was synthesized and evaluated for antimalarial activity. The subsequential synthetic pathways, which included the alkylation of thiols and simultaneous sulfide oxidation and imination, yielded a library of sulfoximine derivatives 3a-s. These were coupled with brominated-isoxazoles 6a-c, to give sulfoximine-isoxazole hybrids 7a-v and further derivatized to compounds 8 and 9. The hybrid compounds were then investigated for their antiplasmodial activity against the wild-type drug-sensitive strain (NF54) and multidrug-resistant strain (K1). Only six (6) hybrids showed minor potency against the drug-sensitive and drug-resistant strains (IC50 values ranging between 4.1 and 5.8 μM). The selectivity studies indicated no significant toxicity of the hybrid compounds against mammalian cells.

Keywords

• Sulfoximine
• Isoxazole
• Antimalarial
• Antiplasmodial
• Sulfoximine-isoxazole hybrids