PT4 is a treatment agent for Cutaneous leishmaniasis (CL). PT4 decreases of mitochondrial membrane potential and increases reactive oxygen species production, therefore leads to parasite death. PT4 is effective against both species of Leishmania. The IC50 values of PT4 against L. amazonensis and L. braziliensis are 125.18 and 233.18 μM , respectively. PT4 also shows potent anti-inflammatory activity in vivo [1].

PT4 (0-1256.5 μM, 48 hours) can inhibit mammalian cells viability [1]. PT4 (314.1-19.6 μM, 48 hours) inhibits the growth of promastigote and amastigote of L. amazonensis and L. braziliensis promastigotes [1]. PT4 causes depolarization of the mitochondrial membrane of L. amazonensis and L. braziliensis promastigotes and increasing ROS in mitochondria [1]. Cell Cytotoxicity Assay [1] Cell Line: Balb/c mice peritoneal exudate (mPEC), J774A.1 macrophages, Fibroblasts Concentration: 0-1256.5 μM Incubation Time: 48 hours Result: Inhibited mPEC, J774A.1 and fibroblasts with CC 50 value of 981.37 μM, 521.47 μM and 895.17 μM, respectively. Cell Proliferation Assay [1] Cell Line: L. amazonensis, L. braziliensis promastigotes Concentration: 314.1-19.6 μM Incubation Time: 48 hours Result: Inhibited promastigote of L. amazonensis and L. braziliensis promastigotes with IC 50 value of 70.46 μM and 181.73 μM, respectively. Inhibited amastigote of them with IC 50 value of 125.18 μM and 233.18 μM, respectively.

The pharmacokinetic and toxicological parameters of PT4 Parameter HBA (≤10) 4 HBD (≤5) 0 LogP (≤5) 2.23 MW (≤500) g/mol 318.33 n-ROTB (≤10) 4 TPSA (A2) 68.09 BBB Yes GIA High P-GP substrate No Skin permeability (cm/s) -6.85 CYP450 2C9 inhibitor Yes CYP450 2D6 inhibitor No CYP450 2C19 inhibitor Yes CYP450 3A4 inhibitor No CYP450 1A2 inhibitor Yes Total Clearance (log ml/min/kg) 0.117 Renal OCT2 substrate No LD50 (mg/Kg) 4700