Concanavalin A, lectin from Canavalia ensiformis seeds has Leishmania infantum antipromastigote activity mediated by carbohydrate recognition domain

Chem Biol Interact. 2024 Aug 25:399:111156. doi: 10.1016/j.cbi.2024.111156. Epub 2024 Jul 18.

Abstract

Leishmaniases, caused by Leishmania parasites, are widespread and pose significant health risks globally. Visceral leishmaniasis (VL) is particularly prevalent in Brazil, with high morbidity and mortality rates. Traditional treatments, such as pentavalent antimonials, have limitations due to toxicity and resistance. Therefore, exploring new compounds like lectins is crucial. Concanavalin A (ConA) has shown promise in inhibiting Leishmania growth. This study aimed to evaluate its leishmanicidal effect on L. infantum promastigotes and understand its mechanism of action. In vitro tests demonstrated inhibition of promastigote growth when treated with ConA, with IC50 values ranging from 3 to 5 μM over 24-72 h. This study suggests that ConA interacts with L. infantum glycans. Additionally, ConA caused damage to the membrane integrity of parasites and induced ROS production, contributing to parasite death. Scanning electron microscopy confirmed morphological alterations in treated promastigotes. ConA combined with the amphotericin B (AmB) showed synergistic effects, reducing the required dose of AmB, and potentially mitigating its toxicity. ConA demonstrated no cytotoxic effects on macrophages, instead stimulating their proliferation. These findings reinforce that lectin exhibits promising leishmanicidal activity against L. infantum promastigotes, making ConA a potential candidate for leishmaniasis treatment.

Keywords: Lectins; Leishmaniasis; Visceral leishmaniasis.

MeSH terms

  • Amphotericin B / pharmacology
  • Animals
  • Antiprotozoal Agents* / chemistry
  • Antiprotozoal Agents* / pharmacology
  • Canavalia*
  • Concanavalin A* / pharmacology
  • Lectins / chemistry
  • Lectins / metabolism
  • Lectins / pharmacology
  • Leishmania infantum* / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / parasitology
  • Mice
  • Plant Lectins / chemistry
  • Plant Lectins / pharmacology
  • Reactive Oxygen Species / metabolism
  • Seeds / chemistry

Substances

  • Concanavalin A
  • Antiprotozoal Agents
  • Reactive Oxygen Species
  • Amphotericin B
  • Lectins
  • Plant Lectins