The Potential of Traditional Knowledge to Develop Effective Medicines for the Treatment of Leishmaniasis

Passero, Luiz Felipe Domingues; Brunelli, Erika dos Santos; Sauini, Thamara; Pavani, Thais Fernanda Amorim; Jesus, Jéssica Adriana; Rodrigues, Eliana

doi:10.3389/fphar.2021.690432

Cited by 22 publications

(18 citation statements)

References 116 publications

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“…Plants are important sources of active principles against Leishmania as shown by a study in Pakistan that reported that 23 plants were tested, using mostly leaves of the genus Lamiaceae and, out of these plants, only 11 were tested in vitro with good results regarding inhibition of the parasite [16]. Another study which also mostly used leaves indicated that among the plants most used by folk medicine to treat leishmaniasis were Carica papaya (Caricaceae), Cedrela odorata (Meliaceae), Musa paradisiaca (Musaceae), and Nicotiana tabacum (Solanaceae) [17]. A study in Mexico showed that dichloromethane and dichloromethane/methanol extracts of Schinus molle, dichloromethane of Lantana camara, and aqueous extracts of Prosopis laevigata had an inhibitory effect on Leishmania amazonensis, although this study also tested aqueous, dichloromethane and dichloromethane/methanol extracts of the leaves and branches of P. guajava against L. amazonensis; and no active or speci c effect was observed [18].…”

Section: Resultsmentioning

confidence: 99%

Antiparasitic effect of Psidium guajava on promastigotes and axenic amastigotes of Leishmania

Rojas‐Jaimes

Mesía-Guevara

Rojas-Puell

et al. 2022

Preprint

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Background: Leishmaniasis is a stigmatic and mutilating disease due to pathogenic species of the genus Leishmania which, depending on the species and the individual's immune status, may vary clinically from a cutaneous, mucosal, and visceral form, and for which there is no suitable treatment without significant side effects. Methods: The method of [3-(3,4 -dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] was used to study the antiparasitic effects of ethanolic (100mg/mL) and aqueous (100mg/mL) extracts of Psidium guajava on axenic amastigotes cultures (8.1 x103 parasite/mL) and promastigotes (12 x 104 parasite/mL) obtained from a patient with cutaneous leishmaniasis, and the percentage of parasite death was evaluated in comparison with Glucantime (300mg/mL) and untreated parasite cultures. Results: Regarding parasite death in promastigotes, the ethanolic and aqueous extracts had a percentage of 22.58% and -45.16%, respectively, with no significant difference between treatments (N=3) (p= 0.058). In contrast, the ethanolic and aqueous extracts had an antiparasitic percentage of 91.67% and -70.83%, respectively, with a significant difference between treatments (N=3) (p<0.05). Conclusions:Our study showed high and significant effectiveness in parasite death (91.67%) of Leishmania axenic amastigotes of the ethanolic extract (100mg/mL) of Psidium guajava, being this result promising and the basis for in vivo studies, using the ethanolic extraction of P. guajava.

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Section: Resultsmentioning

confidence: 99%

Antiparasitic effect of Psidium guajava on promastigotes and axenic amastigotes of Leishmania

Rojas‐Jaimes

Mesía-Guevara

Rojas-Puell

et al. 2022

Preprint

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“…(2S,3R,4R)-3-Hydroxy-4-methyl-2-(n-eicosanil)butanolide (3). Amorphous white solid, 100% purity by HPLC.…”

Section: Extraction and Isolationmentioning

confidence: 99%

“…The treatment of leishmaniasis is limited and involves using toxic drugs such as antimonial derivatives, amphotericin B, and miltefosine. Based on this scenario, the search for new hit compounds is crucial, and natural products can provide inspiring molecules for drug discovery studies against this neglected tropical diseases [2,3].…”

Section: Introductionmentioning

confidence: 99%

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Antileishmanial Effects of Acetylene Acetogenins from Seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives

et al. 2022

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As part of our continuous studies involving the prospection of natural products from Brazilian flora aiming at the discovery of prototypes for the development of new antiparasitic drugs, the present study describes the isolation of two natural acetylene acetogenins, (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-yn-19′-enyl)butanolide (1) and (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-ynyl)butanolide (2), from the seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae). Using an ex-vivo assay, compound 1 showed an IC50 value of 29.9 μM against the intracellular amastigote forms of Leishmania (L.) infantum, whereas compound 2 was inactive. These results suggested that the terminal double bond plays an important role in the activity. This effect was also observed for the semisynthetic acetylated (1a and 2a) and eliminated (1b and 2b) derivatives, since only compounds containing a double bond at C-19 displayed activity, resulting in IC50 values of 43.3 μM (1a) and 23.1 μM (1b). In order to evaluate the effect of the triple bond in the antileishmanial potential, the mixture of compounds 1 + 2 was subjected to catalytic hydrogenation to afford a compound 3 containing a saturated side chain. The antiparasitic assays performed with compound 3, acetylated (3a), and eliminated (3b) derivatives confirmed the lack of activity. Furthermore, an in-silico study using the SwissADME online platform was performed to bioactive compounds 1, 1a, and 1b in order to investigate their physicochemical parameters, pharmacokinetics, and drug-likeness. Despite the reduced effect against amastigote forms of the parasite to the purified compounds, different mixtures of compounds 1 + 2, 1a + 2a, and 1b + 2b were prepared and exhibited IC50 values ranging from 7.9 to 38.4 μM, with no toxicity for NCTC mammalian cells (CC50 > 200 μM). Selectivity indexes to these mixtures ranged from >5.2 to >25.3. The obtained results indicate that seeds of Porcelia macrocarpa are a promising source of interesting prototypes for further modifications aiming at the discovery of new antileishmanial drugs.

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“…Around 25 drugs or combinations have been used for humans in leishmaniasis [22][23][24]. This high number suggests that there are limitations in the currently available chemotherapy.…”

Section: Chemotherapy Of Leishmaniasis: Current Drugs Limitations And...mentioning

confidence: 99%

Antileishmanial Drug Discovery and Development: Time to Reset the Model?

et al. 2021

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Leishmaniasis is a vector-borne parasitic disease caused by Leishmania species. The disease affects humans and animals, particularly dogs, provoking cutaneous, mucocutaneous, or visceral processes depending on the Leishmania sp. and the host immune response. No vaccine for humans is available, and the control relies mainly on chemotherapy. However, currently used drugs are old, some are toxic, and the safer presentations are largely unaffordable by the most severely affected human populations. Moreover, its efficacy has shortcomings, and it has been challenged by the growing reports of resistance and therapeutic failure. This manuscript presents an overview of the currently used drugs, the prevailing model to develop new antileishmanial drugs and its low efficiency, and the impact of deconstruction of the drug pipeline on the high failure rate of potential drugs. To improve the predictive value of preclinical research in the chemotherapy of leishmaniasis, several proposals are presented to circumvent critical hurdles—namely, lack of common goals of collaborative research, particularly in public–private partnership; fragmented efforts; use of inadequate surrogate models, especially for in vivo trials; shortcomings of target product profile (TPP) guides.

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The Potential of Traditional Knowledge to Develop Effective Medicines for the Treatment of Leishmaniasis

Cited by 22 publications

References 116 publications

Antiparasitic effect of Psidium guajava on promastigotes and axenic amastigotes of Leishmania

Antiparasitic effect of Psidium guajava on promastigotes and axenic amastigotes of Leishmania

Antileishmanial Effects of Acetylene Acetogenins from Seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives

Antileishmanial Drug Discovery and Development: Time to Reset the Model?

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