Abstract
This study aimed to appraise the anti-leishmanial potentials of benzoic acid derivatives, including methyl 3,4-dihydroxybenzoate (compound 1) and octadecyl benzoate (compound 2), isolated from the ethnomedicinally important plant Ifloga spicata (I. spicata). Chemical structures were elucidated via FT-IR, mass spectrometry, and multinuclear (1H and 13C) NMR spectroscopy. Anti-leishmanial potentials of the compounds were assessed using Leishmania tropica promastigotes. Moreover, acridine orange fluorescent staining was performed to visualize the apoptosis-associated changes in promastigotes under a fluorescent microscope. A SYTOX assay was used to check rupturing of Leishmania promastigote cell membranes using 0.1% Triton X-100 as positive control. A DNA interaction assay was carried out to assess DNA attachment potential. AutoDock software was used to check the binding affinity of compounds with surface enzyme leishmanolysin gp63 (1LML). Both compounds exhibited considerable anti-leishmanial potential, with LD50 values of 10.40 ± 0.09 and 14.11 ± 0.11 μg/mL for compound 1 and compound 2, respectively. Both compounds showed higher binding affinity with the leishmanolysin (gp63) receptor/protease of Leishmania, as assessed using computational analysis. The binding scores of compounds 1 and 2 with target gp63 were −5.3 and −5.6, respectively. The attachment of compounds with this receptor resulted in their entry into the cell where they bound with Leishmania DNA, causing apoptosis. The results confirmed that the investigated compounds have anti-leishmanial potential and are potential substitutes as natural anti-leishmanial agents against L. tropica.
Highlights
Leishmaniasis is a major health threat affecting more than 350 million people across the globe and resulting in 70,000 deaths per year [1,2,3,4]
A literature survey showed that no plant-derived compound has been approved against leishmaniasis because the rate of isolation of pure compounds from extracts was low, and most of the research was confined to extracts/fractions of plants
Some phytochemicals, like methyl curine, chondrocurine, and coumarin, have exhibited significant results against leishmaniasis, but no mechanistic or in vivo studies have been performed to date
Summary
Leishmaniasis is a major health threat affecting more than 350 million people across the globe and resulting in 70,000 deaths per year [1,2,3,4]. Mainly initiated by Leishmania tropica, is most common in the Northern Areas of Pakistan, and is spreading throughout the country due to the migration of several million refugees [6,7]. This condition is usually self-healing, within 3–18 months, but may sometimes be chronic, and the wounds leave disfiguring spots which lead to public separation and mental pressure. The rational search for new anti-leishmanial agents can replace the need for current chemotherapies, including those based on antimonial and amphotericin B, which have many undesirable side effects [10,11,12]
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