Antileishmanial effects of Sargassum vulgare products and prediction of trypanothione reductase inhibition by fucosterol

Abstract

Aim: To investigate the antileishmanial potency of Sargassum vulgare C. Agardh-derived products and the in silico inhibition of trypanothione reductase by fucosterol. Materials & methods: Sargassum vulgare crude extract and its derived fractions, subfractions and fucosterol were screened against Leishmania major and Leishmania donovani using the MTS and trypanothione reductase colorimetric assays. Macrophages viability was evaluated using the resazurin assay. The inhibition of trypanothione reductase by fucosterol was predicted in silico. Results: The crude extract, fractions 2, 4 and 7, subfractions 8.2 and 8.3 and fucosterol-exhibited antileishmanial activity on promastigote (IC ₅₀ = 18.99–156.02 μg/ml), while fraction 1, subfraction 8.2 and fucosterol were active on L. major and L. donovani amastigote (IC ₅₀ = 18.47–65.34 μg/ml) with low cytotoxicity. Interestingly, fucosterol showed the best activity against both parasites (IC ₅₀ = 18.47–58.21 μg/ml). Strong binding affinities were recorded between fucosterol and Leishmania spp. trypanothione reductases. Conclusion: Fucosterol, which was abundant in S. vulgare, might be responsible for the antileishmanial activity.

Lay abstract

The limited efficacy and severe side effects of current treatment regiments against leishmaniasis highlight the need for new and safer therapies. In line with this, the ability of S. vulagare to prevent the growth of Leishmania parasites was investigated. It was revealed that S. vulagare and its derived products, including fucosterol, showed promising antileishmanial potency. In addition, virtual analysis of fucosterol demonstrated its capacity to strongly bind to Leishmania major and Leishmania donovani trypanothione reductase, putatively linking the antileishmanial activity of fucosterol and the inhibition of trypanothione reductase.