N‑Myristoyltransferase Inhibitors as a Potential Starting Point for the Development of Antischistosomal Agents

Schistosomiasis remains a major global health challenge,
and the
threat of emerging praziquantel resistance highlights the need for
new therapeutic strategies. Here, the Schistosoma mansoni
N-myristoyltransferase was evaluated as a potential drug
target. Six reported NMT inhibitors were tested for SmNMT inhibition and binding, with two compounds showing low nanomolar
potency. These also inhibited NMT of S. hematobium and S. japonicum, and exhibit favorable drug-like
physicochemical properties. In addition, antiparasitic activity against
newly transformed schistosomula and adult worms was
investigated. The results confirm NMT as a viable target for drug
discovery against schistosomiasis and provide a basis for further
optimizations of SmNMT inhibitors.