Abstract:BackgroundConsidering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market.MethodsIn this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.) infantum and its in vitro and in vivo activity.ResultsThe evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular for… Show more
“…Based on the obtained results in this study, it is possible to suggest that both compounds 1 and 2 are interesting prototypes for the development of new drugs, since these molecules were more selective than the standard drug miltefosine, showing a selective index of 3. Other works found a different range of miltefosine SI against Leishmania species that basically is dependent on the parasite specie, strain and number of parasites in the assays among other reasons.…”
Objective This work describes the isolation of anti-Leishmania amazonensis metabolites from Saururus cernuus (Saururaceae). Additionally, ultrastructural changes in promastigotes were evidenced by electron microscopy. Methods The MeOH extract from the leaves of S. cernuus was subjected to bioactivity-guided fractionation. Anti-L. amazonensis activity of purified compounds was performed in vitro against promastigote and amastigote forms. Key findings Bioactivity-guided fractionation of the MeOH extract from the leaves of S. cernuus afforded two related tetrahydrofuran dineolignans: threo, threo-manassantin A (1) and threo,erythro-manassantin A (2). Compounds 1 and 2 displayed activity against promastigotes (EC 50 of 35.4 AE 7.7 and 17.6 AE 4.2 lM, respectively) and amastigotes (EC 50 of 20.4 AE 1.9 and 16.0 AE 1.1 lM, respectively), superior to that determined for the positive control miltefosine (EC 50 of 28.7 AE 3.5 lM). Reduced cytotoxicity for host cells was observed for both compounds. Additionally, ultrastructural changes in promastigotes leading to an alteration of structural morphology were observed, as evidenced by electron microscopy. Furthermore, these compounds altered the morphology and physiology of the plasmatic membrane of L. amazonensis. Conclusions The obtained results indicated that dineolignans 1 and 2 could be considered as a scaffold for the design of novel and selective drug candidates for the treatment of leishmaniasis.
“…Based on the obtained results in this study, it is possible to suggest that both compounds 1 and 2 are interesting prototypes for the development of new drugs, since these molecules were more selective than the standard drug miltefosine, showing a selective index of 3. Other works found a different range of miltefosine SI against Leishmania species that basically is dependent on the parasite specie, strain and number of parasites in the assays among other reasons.…”
Objective This work describes the isolation of anti-Leishmania amazonensis metabolites from Saururus cernuus (Saururaceae). Additionally, ultrastructural changes in promastigotes were evidenced by electron microscopy. Methods The MeOH extract from the leaves of S. cernuus was subjected to bioactivity-guided fractionation. Anti-L. amazonensis activity of purified compounds was performed in vitro against promastigote and amastigote forms. Key findings Bioactivity-guided fractionation of the MeOH extract from the leaves of S. cernuus afforded two related tetrahydrofuran dineolignans: threo, threo-manassantin A (1) and threo,erythro-manassantin A (2). Compounds 1 and 2 displayed activity against promastigotes (EC 50 of 35.4 AE 7.7 and 17.6 AE 4.2 lM, respectively) and amastigotes (EC 50 of 20.4 AE 1.9 and 16.0 AE 1.1 lM, respectively), superior to that determined for the positive control miltefosine (EC 50 of 28.7 AE 3.5 lM). Reduced cytotoxicity for host cells was observed for both compounds. Additionally, ultrastructural changes in promastigotes leading to an alteration of structural morphology were observed, as evidenced by electron microscopy. Furthermore, these compounds altered the morphology and physiology of the plasmatic membrane of L. amazonensis. Conclusions The obtained results indicated that dineolignans 1 and 2 could be considered as a scaffold for the design of novel and selective drug candidates for the treatment of leishmaniasis.
“…The efficacies of the repositioned drugs described in the studies were varied. Pinto and Tempone (2018) reported the in vitro efficacy of amiodarone against intracellular L. infantum promastigote and amastigote forms, partly due to its antagonistic activity in calcium channels. In vivo assays in young hamsters orally treated with amiodarone at 50 and 100 mg/kg/day did not show statistically significant results.…”
Considered prevalent in many countries on five continents, especially in low‐income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.
“…Amiodarone is a potent antiarrhythmic whose anti-leishmanial activity was reported recently in different studies 47 , 48 . The mechanisms of action as an anti-leishmanial are inhibition of sterol biosynthesis, destabilization of Ca 2+ homeostasis, the collapse of mitochondrial membrane potential, and production of reactive oxygen species 49 , 50 .…”
Leishmaniasis is a neglected tropical disease caused by species of
Leishmania,
with a broad spectrum of clinical manifestations, such as cutaneous, visceral, and mucocutaneous presentations. Many drugs are used for its treatment, and a current effective one is a pentavalent antimonial, especially in developing countries. In this review, we discuss recent proposed therapies as well as their side effects.
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