Synthesis and Antimalarial Evaluation of [1, 2,3]‐Triazole‐Tethered Sulfonamide‐Berberine Hybrids

Abstract Malaria still remains a global health problem despite of the availability of effective control and treatment measures. In the present study, a novel series of [1, 2,3]‐triazole tethered sulfonamide‐berberine hybrids were synthesized in good yields via Huisgen [3+2] cycloaddition reaction of various primary, secondary and tertiary sulfonamide based azides with 9‐O‐(propyne)berberine chloride in t ‐BuOH:water (1:1) mixture containing a catalytic amount of sodium ascorbate and CuSO 4 .5H 2 O at 90 o C. After spectroscopic characterization, these novel hybrids were evaluated for their potency against asexual erythrocytic stages of P. falciparum (3D7) in vitro. Most of the synthesized compounds have shown significant antimalarial activity with IC 50 values in the range of 0.1‐20 μg/mL and were also found to be non‐cytotoxic under tested conditions.