The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis

Bezerra-Souza, Adriana; Yamamoto, Eduardo S.; Laurenti, Márcia Dalastra; Ribeiro, Susan Pereira; Passero, Luiz Felipe Domingues

doi:10.1016/j.parint.2016.08.003

Cited by 16 publications

(7 citation statements)

References 35 publications

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“…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.…”

Section: Resultsmentioning

confidence: 95%

Antileishmanial activity and ultrastructural changes of related tetrahydrofuran dineolignans isolated from Saururus cernuus L. (Saururaceae)

Brito

Passero²,

Bezerra-Souza

et al. 2019

Journal of Pharmacy and Pharmacology

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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.

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Section: Resultsmentioning

confidence: 95%

Antileishmanial activity and ultrastructural changes of related tetrahydrofuran dineolignans isolated from Saururus cernuus L. (Saururaceae)

Brito

Passero²,

Bezerra-Souza

et al. 2019

Journal of Pharmacy and Pharmacology

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“…On the other hand, animals treated with MAFP did not show significant alterations in the course of infection. The inhibitor AA was not assayed in vivo due to its toxicity for animals [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…The inhibitors AA (25.0; 50.0; 100.0 μM), BEL (1.0; 2.0; 4.0 μM) and MAFP (5.0; 10.0; 20.0 μM) were added to the infected cells. As standard treatment, miltefosine’s EC 50 was used [ 14 ]. After 24 h of incubation, infection indexes were estimated [ 15 ] and the concentrations able to decrease the infection index to 50% were estimated via the software GraphPad Prism 5.0.…”

Section: Methodsmentioning

confidence: 99%

Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis

Bordon

Laurenti

Ribeiro

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundLipid metabolites play an important role in parasite differentiation and virulence. Studies have revealed that Leishmania sp. uses prostaglandins to evade innate barriers, thus enabling the parasites to survive inside immune cells. Despite the role of the enzyme Phospholipase A2 (PLA2) in prostaglandins production, few studies have investigated the role of parasite PLA2 during the interaction between L. (L.) amazonensis and the host (in vitro and in vivo) immune cells.MethodsIn the present work, the leishmanicidal effect of PLA2 inhibitors, methyl arachidonyl fluorophosphonate (MAFP), bromoenol lactone (BEL) and aristolochic acid (AA) were investigated in vitro (promastigote and intracellular amastigote forms of L. (L.) amazonensis) and during in vivo infection using BALB/c mice.ResultsThe aforementioned inhibitors were deleterious to promastigote and amastigote forms of the L. (L.) amazonensis and were non-toxic to peritoneal macrophages from BALB/c mice. L. (L.) amazonensis-infected BALB/c mice treated with the inhibitor BEL presented decreased lesion size and skin parasitism; however, BEL treatment induced hepatotoxicity in BALB/c mice.ConclusionsResults presented herein suggested that PLA2 inhibitors altered L. (L.) amazonensis viability. In spite of liver toxicity, treatment with BEL was the most selective compound in vitro, as well in vivo, resulting in lower skin parasitism in the infected mice. These findings corroborate the role of PLA2 in parasite virulence and maintenance in vertebrate hosts, and suggest that molecules structurally related to BEL should be considered when planning compounds against Leishmania sp.

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“…Since leishmania parasites also possess sterols on their cell walls, drugs with capacity to interfere with sterol synthesis such as azoles and allylamines can arguably result in the death of leishmania parasites. 8 Terbinafine and related allylamines can therefore be considered potential drugs for the treatment of leishmaniasis. In a study by Bahamdan et a1, oral terbinafine administered daily for four consecutive weeks cleared cutaneous leishmaniasis in over 70% of treated patients, of note, is that there were no any observable or reported side effects in their study.…”

Section: Discussionmentioning

confidence: 99%

A case of cutaneous leishmaniasis successfully treated with oral terbinafine in Kenya

Mawenzi

2018

Int J Res Dermatol

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<p>Leishmaniasis is a tropical disease of the skin and the reticuloendethelial system caused by a parasite of the genus- <em>Leishmania</em>. The disease poses significant psychosocial and public health burdens in endemic areas. Its treatment poses significant challenges considering that new treatment modalities are currently unavailable. The out-dated and toxic antimonial compounds remain the standard treatment. Nevertheless, these agents are mostly unavailable and reports of resistance to these compounds are increasing. Various drugs have therefore been used off label to treat cutaneous leishmaniasis. Terbinafine, an allylamine designed for treatment of fungal infections has been used off label in the treatment cutaneous leishmaniasis in Middle East and India. However, its potential has not been fully exploited in Kenya. This case is reported of a thirteen year old boy, a resident of a leishmaniasis endemic region in Kenya who presented with a symptomless, well demarcated plaque embedded with crusts and papules on his right cheek. Fine needle aspiration cytology revealed leishmania donovani bodies confirming a diagnosis of cutaneous leishmaniasis. He was treated with oral terbinafine 250mg daily for two consecutive months together with topical application of a combination of 10% Chrotamiton + 2% Sulphur cream applied for three consecutive months. A significant improvement evidenced by substantial flattening of the lesion, conspicuous digital image changes and general clinical improvement was noted after 3 months of follow up. This observation endorses oral terbinafine, as an efficacious management of uncomplicated cutaneous leishmaniasis. To limit scarring, an appropriate topical application can be added to oral terbinafine.</p>

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The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis

Cited by 16 publications

References 35 publications

Antileishmanial activity and ultrastructural changes of related tetrahydrofuran dineolignans isolated from Saururus cernuus L. (Saururaceae)

Antileishmanial activity and ultrastructural changes of related tetrahydrofuran dineolignans isolated from Saururus cernuus L. (Saururaceae)

Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis

A case of cutaneous leishmaniasis successfully treated with oral terbinafine in Kenya

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