Publication date: Dec 01, 2024
Strong antileishmanial and antitrypanosomal activities were highlighted for the crude methanolic extract (IC = 0. 61 and 2. 15 μg/mL, respectively) of Zanthoxylum zanthoxyloides (Lam. ) B. Zepernick & Timler root bark, as well as for its apolar partitions (cyclohexane: IC = 0. 66 and 5. 17 μg/mL, respectively and dichloromethane: IC = 0. 07 and 0. 22 μg/mL, respectively), with a good selectivity index (SI) towards WI-38 cells. In addition, cyclohexane and dichloromethane extracts exhibited a dose-dependent inhibition of human coronavirus HCoV-229E infection in hepatoma Huh-7 cells expressing or not the cellular protease TMPRSS2 (IC values of 5. 29 μg/mL and 4. 87 μg/mL, respectively). Fractionation of these active extracts led to the isolation of a new racemic benzophenanthridine alkaloid named zanthoxyloithrine (1), together with 13 known compounds. Their structures were elucidated by spectroscopic techniques including IR, UV, HR-MS, 1D and 2D NMR and electronic circular dichroism. In parallel, HR-ESI-MS/MS based dereplication and molecular networking analysis were performed to identify unpurified compounds in cyclohexane and dichloromethane extracts. Zanthoxyloithrine (1) showed strong antileishmanial (IC = 0. 14 μM, SI = 52. 0) and antitrypanosomal (IC = 0. 36 μM, SI = 20. 8) activities. In addition, compound (1) demonstrated a high antiviral activity against HCoV-229E with IC value of 6. 70 μM in presence of TMPRRS2 and without significant toxicity on Huh-7 cells. Other purified benzo[c]phenanthridine alkaloids also showed anti-coronavirus and antiparasitic activities.
Semantics
Type | Source | Name |
---|---|---|
disease | MESH | infection |
disease | MESH | hepatoma |
disease | IDO | cell |
disease | MESH | Tumor |