Antileishmanial activity and drug-likeness evaluation of β-carboline derivatives: an integrated in vitro study

Leishmaniasis is a parasitic disease caused by several Leishmania species, including Leishmania (Leishmania) amazonensis, and is associated with oxidative stress and tissue damage. The objective was to evaluate 11 β-carboline derivatives for their predicted toxicity and drug-likeness properties, antileishmanial activity, hemolytic potential, antioxidant capacity. In silico analyses indicated favorable physicochemical parameters, as well as good permeability and solubility profiles. In vitro assays demonstrated antileishmanial activity against promastigotes after 72 h, with IC₅₀ values ranging from 5.15 to 41.19 μM (8) and (5) were the most active compounds. None of the derivatives showed hemolytic activity in human erythrocytes. Antioxidant assays revealed significant free radical scavenging, with (11) showing the highest activity, however all compounds outperformed the control. These findings identify β-carboline derivatives as promising candidates with combined antileishmanial, antioxidant, and low-toxicity profiles. Further studies are warranted to investigate their mechanisms of action and in vivo efficacy.