Abstract
Background: Natural products have been important resources for potential drug development.
Among the many classes of natural products, alkaloids have the most therapeutic applications. Treatment
of leishmaniasis by chemical drugs remains a challenge because of toxic side effects, limited efficacy, and
drug resistance. This review focuses to embrace all researches on leishmanicidal alkaloids over a specific
range of time, with special consideration the molecular mechanism of action, and structure-related activity.
Methods: All publications (in English) from Web of Science, PubMed, Science Direct, Scopus, and
Google Scholar from 2000-2021 using a variety of keywords such as natural alkaloids, herbal alkaloids,
marine alkaloids along with leishmaniasis were included in the present study. In this summary, the focus
is mainly on natural alkaloids of plant, mineral, marine origin, etc., which have empirically demonstrated
the antileishmanial effect.
Results: Fourteen categories of alkaloids with anti-leishmaniasis activity were extracted from the articles.
The highest number of alkaloids belonged to isoquinoline, indole, and quinoline alkaloids (21.78%,
20.67%, and 16.48% respectively). This review indicated that the mentioned alkaloids are able to inhibit
the proliferation of parasites, the respiratory chain and protein synthesis, arrest the cell cycle, disrupt the
mitochondrial membrane integrity, inhibit leishmanial topoisomerase, induce mitochondrial dysfunction,
and changes in the parasite morphology.
Discussion: The present study highlighted antileishmanial alkaloids that are active against different species
of Leishmania in vitro and some of them are also active in visceral and cutaneous leishmaniasis models.
However, more clinical studies are needed to clarify the anti-leishmanial activity of alkaloids against
leishmania in detail.
Conclusion: Among the reported compounds, two main classes of alkaloids including isoquinoline and
indole alkaloids cover a wider range of anti-parasitic compounds, and structure-activity relationships
(SAR) studies of these molecular skeletons may be good lead compounds and afford the structural clues
to develop novel medicines with more selective therapeutic profiles.
Keywords:
Herbal medicine, alkaloids, visceral leishmania, cutaneous leishmaniasis, mechanism of action, isoquinoline, indole alkaloids.
Graphical Abstract
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