Photocatalytic Unsymmetrical Coupling of 2‑Substituted Quinolines: Synthesis and Evaluation of the Antiplasmodial Potential of β‑Norbenzomorphan Frameworks

We
herein report unsymmetrical coupling of 2-methylquinolines under
the blue LED light conditions using iridium-based photocatalyst. This
methodology represents the direct synthetic method for the β-norbenzomorphan
skeleton from the quinoline moiety. The current method is more ecofriendly
and efficient compared to the existing methods as manifested by green
metrics parameters. Substituted quinolines gave the desired products
with good to excellent yields. In vitro study of
isolated compounds against the growth of Plasmodium
falciparum grown in human red blood cells using SYBR
green microtiter plate-based screening showed 2d (chlorine-substituted
imitate) and 2o (CO2Et-substituted imitate)
to have sub-micromolar IC50s against chloroquine-resistant PfINDO strain. In silico docking scores
for binding to falcipain-2 were comparable (2d) or better
(2o) than chloroquine.