Efficacy of Diterpene Polyalthic Acid Combined with Amphotericin B against Leishmania amazonensis In Vitro

<b>Background/Objectives:</b> Leishmaniasis, a neglected disease caused by <i>Leishmania</i> spp. including <i>L. amazonensis</i>, urgently requires new treatments. Polyalthic acid (PA), a natural diterpene from <i>Copaifera</i> spp., has previously demonstrated significant antiparasitic potential. This study evaluated the leishmanicidal effects of polyalthic acid (PA), alone and with amphotericin B (AmpB), on <i>L. amazonensis</i> promastigote and amastigote forms. <b>Results:</b> PA showed significant activity against promastigotes, with 50% effective concentration (EC₅₀) values of 2.01 μM at 24 h and an EC₅₀ of 3.22 μM against amastigotes after 48 h. The PA and AmpB combination exhibited a synergistic effect on both forms without inducing cytotoxicity or hemolysis. Morphological changes in promastigotes, including vacuole formation and cell rounding, were more pronounced with the combination. <b>Conclusions:</b> These findings suggest that PA and AmpB together could form a promising new treatment strategy against <i>Leishmania</i> infections, offering enhanced efficacy without added toxicity.