Antileishmanial, antitrypanosomal and anti-coronavirus activities of benzophenanthridine alkaloids and other specialized metabolites isolated from the root bark of Zanthoxylum zanthoxyloides (Lam.) B.Zepernick & Timler.

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.

Concepts Keywords
Antiparasitic Alkaloids
Bark Alkaloids
Benzocphenanthridine Animals
Coronavirus Anti-coronavirus
Molecular Antileishmanial
Antiprotozoal Agents
Antiprotozoal Agents
Antitrypanosomal
Antiviral Agents
Antiviral Agents
Benzophenanthridine alkaloids
Benzophenanthridines
Benzophenanthridines
Cell Line, Tumor
Humans
Molecular Structure
Phytochemicals
Phytochemicals
Plant Bark
Plant Extracts
Plant Extracts
Plant Roots
Plasmodium falciparum
Root bark
Trypanocidal Agents
Trypanocidal Agents
Trypanosoma brucei brucei
Trypanosoma cruzi
Zanthoxylum

Semantics

Type Source Name
disease MESH infection
disease MESH hepatoma
disease IDO cell
disease MESH Tumor

Original Article

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