Leishmaniasis is a complex of diseases caused by the invasion of protozoan parasites of the genus Leishmania into the mononuclear phagocytic system of mammalian hosts that can compromise viscera, skin and mucosa. This vector-borne disease threatens ∼350 million people worldwide mainly in the tropical and subtropical areas. It is estimated that ∼0.9 and 1.7 million people are infected with 20,000–30,000 deaths per year. Over 90% of new leishmaniasis cases occur in Afghanistan, Algeria, Bangladesh, Bolivia, Brazil, Colombia, Ethiopia, India, Iran, Peru, South Sudan, Sudan and Syria (Desjeux, 2004; WHO - World Health Organization, 2021). Leishmaniasis are one of the neglected poverty related diseases and it is estimated that the majority of infected patients live with less than US$ 1 per day (Alvar et al., 2006).

The diagnosis and effective treatment of patients can reduce the prevalence of the disease (WHO - World Health Organization, 2021). Despite of its limitations, chemotherapeutical treatment still remains as the main control measure for all clinical forms of leishmaniasis (WHO - World Health Organization, 2021). Even though the use of pentavalent antimonials, such as meglumine antimoniate (MA, Glucantime®) and sodium stibogluconate (SSG, Pentostam®), present several limitations, these drugs have been used for more than half a century in the therapy of leishmaniasis as first-line drugs (González et al., 2009; Name et al., 2005).

The large-scale use of antimonials has led to the selection of parasites that have mechanisms of resistance to these drugs. Therefore, other drugs are used for the treatment of leishmaniasis. Main drugs used for the treatment of leishmaniasis are amphotericin b deoxycholate, liposomal amphotericin B, miltefosine and pentamidine (Chappuis et al., 2007; Croft and Coombs, 2003). However, these current antileishmanial agents present several limitations including low efficacy, toxicity, adverse side effects, drug-resistance, long-term treatment and high cost (Kedzierski et al., 2009; Sundar et al., 2012).

In the light of the limitations of the current therapeutic arsenal and strategies, the WHO strongly recommends and supports research into new drugs against leishmaniasis (Ridley, 2003). However, a lack of commercial return from drug development and of political support in the case of neglected diseases, such as leishmaniasis, has resulted in insufficient funding and commitment from both public sector agencies and the pharmaceutical industry (Ridley, 2003). Another factor is that most of the medications used in the treatment of leishmaniasis are not new chemical entities, but reused treatments (Olías-Molero et al., 2021).

In this context, new therapeutic options are being researched for the treatment of leishmaniasis, seeking a more effective and less toxic surgery. Research in the field of vaccine, pharmacological repositioning and rejuvenation, drug association, search for new synthetic and/or natural products derived from flora represents a valid technique in the search for new antileishmanials (Santiago et al., 2021; WHO - World Health Organization, 2021). Indeed, the interest in the investigation of medicinal plants and natural products for the treatment of leishmaniasis and others parasitic diseases has been grown in recent years (Batista et al., 2009; Lima et al., 2015).

Brazil has a great diversity of flora throughout its territory, estimated at around 20% of the total number of species on the planet (Ministry of the Environment Brazil, 2021). The National Policy on Integrative and Complementary Practices (NPICP) was created by the public health system aiming to expand the therapeutic options, with a guarantee of access to medicinal plants, herbal medicines and services related to phytotherapy, with safety, efficacy and quality, from the perspective of integral health care (Saúde, 2006). Several plants are used by native populations, in different regions of the country, to treat various infectious diseases, such as malaria and leishmaniasis (Brito and Brito, 1993; Alves et al., 2000). This popular\traditional knowledge, or ethnopharmacology, may be useful in the search for new active compounds and development of phytomedicines against these diseases, with reduced side effects and low cost.

The present study investigated the in vitro effects of five different natural products isolated from plants, in order to evaluate their activity against L. infantum and L. amazonensis. Their inhibitory concentrations (IC50) against promastigote forms, as well as their cytotoxic effects (CC50) on cells derived from a human primary hepatoblastoma (HepG2), were determined and the selectivity index of each substance was calculated (SI = CC50/IC50).