An insight into tetrahydro-β-carboline-tetrazole hybrids: synthesis and bioevaluation as potent antileishmanial agents.

A series of 2,3,4,9-tetrahydro-β-carboline tetrazole derivatives () have been synthesized utilizing the Ugi multicomponent reaction and were identified as potential antileishmanial chemotypes. Most of the screened derivatives exhibited significant activity against the promastigote (IC from 0.59 ± 0.35 to 31 ± 1.27 μM) and intracellular amastigote forms (IC from 1.57 ± 0.12 to 17.6 ± 0.2 μM) of , and their activity is comparable with standard drugs miltefosine and sodium stibogluconate. The most active compound was further studied against the /golden hamster model at a dose of 50 mg kg through the intraperitoneal route for 5 consecutive days, which displayed 75.04 ± 7.28% inhibition of splenic parasite burden. Pharmacokinetics of compound was studied in the golden Syrian hamster, and following a 50 mg kg oral dose, the compound was detected in hamster serum for up to 24 h. It exhibited a large volume of distribution (651.8 L kg), high clearance (43.2 L h kg) and long mean residence time (10 h).