Leishmania amazonensis response to artemisinin and derivatives. (February 2021)

• Record Type: Journal Article
• Authors: Machín, Laura; Nápoles, Rachel; Gille, Lars; Monzote, Lianet
• Is Part Of: Parasitology international. Volume 80(2021)
• Publication Date: 2021-02
• Subjects: Artemisinin -- artesunate. -- artemether. -- Leishmania amazonensis. -- amastigotes -- BALB/c mice; Arts artemisinin and derivatives -- ART artemisinin -- ASC ascaridole -- ATM artemether -- ATS artesunate -- CC50 medium cytotoxic concentration -- CL cutaneous leishmaniasis -- DeoxyART deoxyartemisinin -- DHA dihydroartemisinin -- DMSO dimethyl sulfoxide -- EP endoperoxide -- GTM Glucantime® -- HAccept hydrogen bond acceptor groups -- HDonor hydrogen bond donor groups -- HFBS heat-inactivated fetal bovine serum -- IC50 medium inhibitory concentration -- MTT 3-[4:5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide -- MW molecular weight -- NTD neglected tropical diseases -- RO5 'rule-of-5' -- SI selectivity index -- SD standard deviation -- VL visceral leishmaniasis -- WHO World Health Organization; Parasitology -- Periodicals; Parasites -- Periodicals; Parasitic Diseases -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; 571.99905
• DOI: 10.1016/j.parint.2020.102218
• Languages: English
• ISSNs: 1383-5769

Abstract

Abstract: The worldwide presence of Leishmania parasites increases in the poorest regions. Current leishmaniasis treatments are unsatisfactory due to resistance development, side effects and cost. Herein, we describe the in vitro activity of artemisinin (ART), artemether (ATM), artesunate (ATS) and dihydroartemisinin (DHA) against Leishmania amazonensis . Selected compounds were assayed in the animal model of cutaneous leishmaniasis in BALB/c mice. On intracellular amastigotes, similar activity ( p > 0.05) was observed for ART, ATM and ATS (IC50 = 15.0–19.2 μM), which were inferior ( p < 0.05) respect to reference endoperoxide ascaridole (IC50 = 11.5 ± 1.0 μM) and superior (p < 0.05) compared with reference drug Glucantime® (IC50 = 30.1 ± 9.0 μM). In contrast, DHA (IC50 = 38.5 ± 4.7 μM) showed higher IC50 values ( p < 0.05) than other artemisinins and ascaridole, but similar ( p > 0.05) than Glucantime®; while deoxyartemisinin caused smaller inhibition (IC50 = 88.9 ± 5.2 μM). Selectivity indexes of >13, 6, 11 and 1 were obtained for ART, ATM, ATS and DHA, respectively. In addition, the potential effect of ART and ATS was also demonstrated in the murine model, causing a significant reduction ( p < 0.05) of the lesion size and parasite load regarding untreated animals and treated with vehicle. Effects of both artemisinins were comparable ( p > 0.05) with Glucantime® and ascaridole-treated mice. In particular, artemisinin is recommended to further studies, which could be an advantage over the ascaridole endoperoxide and could be useful in endemic areas of parasite resistance to antimonials. Graphical abstract: Unlabelled Image Highlights: Artemisinin, artemether and artesunate showed activity against intracellular amastigotes of Leishmania amazonensis in similar range of reference drug Glucantime®. Dyhidroartemisinin and deoxyartemisinin showed higher IC50 values. Artemisinin and artesunate were able to control experimental cutaneous leishmaniasis in BALB/c mice.