Anti-Leishmania activity of artesunate and combination effects with amphotericin B against Leishmania (Mundinia) martiniquensis in vitro

Intakhan, Nuchpicha; Siriyasatien, Padet; Chanmol, Wetpisit

doi:10.1016/j.actatropica.2021.106260

Cited by 3 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Artesunate (ARS) is a more stable derivative with greater solubility from artemisinin. In a recent study, Intakhan et al. (2022) associated ARS e with AmB, with the aim of seeking treatments that minimize the toxicity of AmB.…”

Section: Terpenic Compounds With Anti- Leishmania ...mentioning

confidence: 99%

“…Thus, it was possible to reduce the AmB dose by 9.7 times. This initial study is profoundly relevant as it encourages new less toxic formulations and increases the cure rate of patients in the clinic ( Intakhan et al., 2022 ). Curzerene was originally isolated from the roots of Curcuma longa , however, curzerene is present in various essential oils from different species, including those belonging to the Eugenia genus.…”

Section: Terpenic Compounds With Anti- Leishmania ...mentioning

confidence: 99%

See 1 more Smart Citation

Exploring the leishmanicidal potential of terpenoids: a comprehensive review on mechanisms of cell death

Rodrigues,

Carloto,

Gonçalves

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Leishmaniasis is a neglected tropical disease with a wide spectrum of clinical manifestations, ranging from visceral to cutaneous, with millions of new cases and thousands of deaths reported each year. The species of Leishmania and the immune response of the host determine the severity of the disease. Leishmaniasis remains challenging to diagnose and treat, and there is no vaccine available. Several studies have been conducted on the use of herbal medicines for the treatment of leishmaniasis. Natural products can provide an inexhaustible source of chemical diversity with therapeutic potential. Terpenes are a class of natural products derived from a single isoprene unit, a five-carbon compound that forms the basic structure of isoprenoids. This review focuses on the most important and recent advances in the treatment of parasites of the genus Leishmania with different subclasses of terpenes. Several mechanisms have been proposed in the literature, including increased oxidative stress, immunomodulatory role, and induction of different types of parasite cell death. However, this information needs to be brought together to provide an overview of how these compounds can be used as therapeutic tools for drug development and as a successful adjuvant strategy against Leishmania sp.

show abstract

Section: Terpenic Compounds With Anti- Leishmania ...mentioning

confidence: 99%

Section: Terpenic Compounds With Anti- Leishmania ...mentioning

confidence: 99%

Exploring the leishmanicidal potential of terpenoids: a comprehensive review on mechanisms of cell death

Rodrigues,

Carloto,

Gonçalves

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Artesunate is a semisynthetic compound currently applied for the treatment of malaria using various pharmaceutical forms [ 1 , 2 ]. Moreover, it has a broad therapeutic potential, such as anticancer activity [ 3 – 7 ] as well as inhibitory effects against schistosomiasis [ 8 ], leishmaniasis [ 9 ], Mycobacterium tuberculosis [ 10 ], and viral infections [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Degradation kinetics of artesunate for the development of an ex-tempore intravenous injection

Gashe

Wynendaele

Spiegeleer

et al. 2022

Malar J

View full text Add to dashboard Cite

Background Artesunate is recommended by the World Health Organization (WHO) for parenteral treatment of severe Plasmodium falciparum malaria. However, artesunate is inherently unstable in an aqueous solution and hydrolyses rapidly after its preparation for injection. Therefore, the aim of the study was to evaluate the stabilizing effects of phosphate buffer and mannitol against short-term (ex-tempore) artesunate hydrolysis. Methods A HPLC–UV isocratic method was developed using a reversed-phase fused core column (HALO RP-C18) and a mobile phase consisting of a mixture of 45% ammonium formate 10 mM in water (pH 4.5) and 55% methanol. Artesunate was formulated as aqueous solutions using a design of experiment (DOE) to investigate the artesunate stabilizing effects of pH (8–10), phosphate buffer strength (0.3–0.5 M), and mannitol (0–0.22 mmol/mL). The solutions were incubated at predefined temperatures (5, 25, and 40 °C) with subsequent analysis. Arrhenius equation was applied to model and evaluate the stability results. Results The developed HPLC-based method using fused-core stationary phase allowed to selectively quantify artesunate in the presence of its main hydrolysis degradants; namely β-dihydroartemisinin (β-DHA) and α-dihydroartemisinin (α-DHA) within 10 min. By applying the Arrhenius equation, the rate of hydrolysis of the drug increased approximately by 3.4 as the temperature raised by 10 °C. Buffer strength was found to be the main factor affecting the hydrolysis rate constants at 5 and 25 °C (p < 0.05), the activation energy (p = 0.009), and the frequency factor (p = 0.045). However, the effect of the buffer was predominant on the activation energy and hydrolysis rate constants, revealing its stabilizing effect on the drug at lower buffer strength (0.3 M). Within the investigated range (pH = 8–10), pH was found to influence the activation energy, with a positive stabilizing effect in the pH range of 8–9. The addition of mannitol as stabilizing agent into artesunate aqueous formulation did not show an improved response. Conclusion Phosphate buffer was the main stability determining factor of artesunate in the aqueous intravenous (i.v.) formulation and was found to be more effective in stabilizing artesunate at a buffer strength of 0.3 M in pH 8–9, while mannitol lacked stabilizing effect.

show abstract

“…Artesunate is a semisynthetic compound currently applied for the treatment of malaria using various pharmaceutical forms [1,2]. Moreover, it has a broad therapeutic potential, such as anticancer activity [3][4][5][6][7] as well as inhibitory effects against schistosomiasis [8], leishmaniasis [9], Mycobacterium tuberculosis [10], and viral infections [11,12].…”

Section: Introductionmentioning

confidence: 99%

Degradation kinetics of artesunate for the development of an ex-tempore intravenous injection

Gashe

Wynendaele

Spiegeleer

et al. 2022

Preprint

View full text Add to dashboard Cite

BackgroundArtesunate is recommended by the world health organization (WHO) for parenteral treatment of severe Plasmodium falciparum malaria. However, artesunate is inherently unstable in an aqueous solution and hydrolyses rapidly after its preparation for injection. Therefore, the aim of the study was to evaluate the stabilizing effects of phosphate buffer and mannitol against short-term (ex-tempore) artesunate hydrolysis.MethodsA HPLC-UV isocratic method was developed using a reversed-phase fused core column (HALO RP-C18) and a mobile phase consisting of a mixture of 45% ammonium formate 10 mM in water (pH 4.5) and 55% methanol. Artesunate was formulated as aqueous solutions using a design of experiment (DOE) to investigate the artesunate stabilizing effects of pH (8-10), phosphate buffer strength ( 0.3 – 0.5 M), and mannitol (0 – 0.22 mmol/mL). The solutions were incubated at predefined temperatures (5, 25, and 40 °C) with subsequent analysis. Arrhenius equation was applied to model and evaluate the stability results.ResultsThe developed HPLC-based method using fused-core stationary phase allowed to selectively quantify artesunate in the presence of its main hydrolysis degradants; namely β-dihydroartemisinin (β-DHA) and α-dihydroartemisinin (α-DHA) within 10 minutes. By applying the Arrhenius equation, the rate of hydrolysis of the drug increased approximately by 3.44 as the temperature raised by 10 ℃. Buffer strength was found to be the main factor affecting the hydrolysis rate constants at 5 and 25 ℃ (p<0.05), the activation energy (p = 0.007), and the frequency factor (p = 0.046). However, the effect of the buffer was predominant on the activation energy and hydrolysis rate constants, revealing its stabilizing effect on the drug at lower buffer strength (0.3 M). Within the investigated range (pH = 8-10), pH was found to influence the activation energy, with a positive stabilizing effect in the pH range of 8-9. The addition of mannitol as stabilizing agent into artesunate aqueous formulation did not show an improved response. ConclusionPhosphate buffer was the main stability determining factor of artesunate in the aqueous intravenous (i.v.) formulation and was found to be more effective in stabilizing artesunate at a buffer strength of 0.3 M in pH 8 to 9, while mannitol lacked stabilizing effect.

show abstract

Anti-Leishmania activity of artesunate and combination effects with amphotericin B against Leishmania (Mundinia) martiniquensis in vitro

Cited by 3 publications

References 37 publications

Exploring the leishmanicidal potential of terpenoids: a comprehensive review on mechanisms of cell death

Exploring the leishmanicidal potential of terpenoids: a comprehensive review on mechanisms of cell death

Degradation kinetics of artesunate for the development of an ex-tempore intravenous injection

Degradation kinetics of artesunate for the development of an ex-tempore intravenous injection

Contact Info

Product

Resources

About