Leishmanicidal effect of dinoponeratoxin peptides from Dinoponera quadriceps

Leishmaniasis, caused by protozoa of the genus Leishmania, remains a major global public health concern, with an estimated 30,000 deaths annually. Toxicity and emerging resistance to first-line therapies have hindered disease control. Arthropod antimicrobial peptides (AMPs) represent a promising source of novel therapeutic alternatives. Dinoponeratoxins from the venom of the ant Dinoponera quadriceps have demonstrated notable antimicrobial and trypanocidal activities. This study evaluated the leishmanicidal potential of dinoponeratoxins M-PONTX-Dq3a, M-PONTX-Dq3b and M-PONTX-Dq3c. The treatment with M-PONTX-Dq3a showed the best results in L. braziliensis infection, exhibiting leishmanicidal activity against both parasite forms, increasing TNF-α and nitrite production in macrophages and inducing apoptosis in promastigotes. These findings support M-PONTX-Dq3a as a potential biopharmaceutical candidate for leishmaniasis treatment.