Echinococcosis
is a global public health issue that generally occurs
in areas with developed animal husbandry. In search of safe and effective
therapeutic agents against echinococcosis, we designed and synthesized
new 1,3-substituted β-carboline derivatives based on harmine.
Among them, compounds 1a, 1c, and 1e displayed potent inhibitory activity against Echinococcus granulosus in vitro, significantly better than albendazole and harmine. The morphological
detection revealed that 1a, 1c, and 1e significantly changed the ultrastructure of Echinococcus granulosus protoscolices (PSCs). Furthermore,
pharmacokinetic studies suggested that 1a possessed a
better metabolic property. Encouragingly, 1a exhibited
a highest cyst inhibition rate as 76.8% in vivo and
did not display neurotoxicity in mice. Further mechanistic research
illustrated that 1a has the potential to induce autophagy
in PSCs, which may be responsible for the therapeutic effect of the
drugs. Together, 1a could be a promising therapeutic
agent against echinococcosis, warranting further study.