scholarly journals Hydrazone Derivatives Enhance Antileishmanial Activity of Thiochroman-4-ones

2017 ◽  
Author(s):  
Esteban Vargas ◽  
Fernando Echeverri ◽  
Yulieth A. Upegui ◽  
Sara M. Robledo ◽  
Wiston Quiñones
Keyword(s):  
High Selectivity ◽  
Skin Lesions ◽  
Antileishmanial Activity ◽  
Intracellular Amastigotes ◽  
Acyl Hydrazone ◽  
Leishmania Panamensis ◽  
Antileishmanial Activities ◽  
Derivatives Of ◽  
Leishmania Parasites

Cutaneous Leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, treatment can be complex and prolonged, high toxicity, side effects and high cost, there is an urgent need to develop alternatives for the treatment for CL that may have different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against intracellular amastigotes form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2); our results show that derivatization with acyl hydrazones significantly enhance the antileishmanial activity, among the compounds tested semicarbazone (19) and thiosemicarbazone (20) derivatives of thioflavanone display the highest antileishmanial activities with EC50 values of 5.4 and 5.1 µM both with low cytotoxicities, 100.2 a 50.1 µM resulting in high selectivity index (SI).

scholarly journals Hydrazone Derivatives Enhance Antileishmanial Activity of Thiochroman-4-ones

2018 ◽  
Author(s):  
Esteban Vargas ◽  
Fernando Echeverri ◽  
Yulieth A. Upegui ◽  
Sara M. Robledo ◽  
Wiston Quiñones
Keyword(s):  
Skin Lesions ◽  
Mechanisms Of Action ◽  
Antileishmanial Activity ◽  
Acyl Hydrazone ◽  
Leishmania Panamensis ◽  
Antileishmanial Activities ◽  
Derivatives Of ◽  
Intracellular Amastigote ◽  
Leishmania Parasites

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC50 values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).

scholarly journals Leishmanicidal and Cytotoxic Activities of Extracts and Naturally-Occurring Compounds from two Lauraceae Species

2011 ◽  
Vol 6 (2) ◽  
pp. 1934578X1100600
Author(s):  
Jeysson Sánchez-Suárez ◽  
Ericsson Coy-Barrera ◽  
Luis Enrique Cuca ◽  
Gabriela Delgado
Keyword(s):  
Leishmania Species ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Activities ◽  
Naturally Occurring ◽  
Ethanolic Extracts ◽  
Leishmania Panamensis ◽  
J774 Cells ◽  
Different Levels ◽  
Leishmania Parasites

The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-otobaphenol (14), was found to be the most selective compound on L. panamensis.

Antileishmanial activities of leaf latex and compound isolated from Aloe ghibensis Sebsebe & Friis

2020 ◽  
Vol 35 (1) ◽  
pp. 51-58
Author(s):  
Tamirat Tekassa ◽  
Yitagesu Tewabe ◽  
Daniel Bisrat ◽  
Asrat Hailu ◽  
Kaleab Asres
Keyword(s):  
Leishmania Donovani ◽  
Leishmania Species ◽  
2D Nmr ◽  
Antileishmanial Activity ◽  
Spectroscopic Techniques ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Phytochemical Constituents ◽  
Antileishmanial Activities

Aloe ghibensis Sebsebe & Friis is traditionally used in Ethiopia for the treatment of various ailments including skin problem, wounds and malaria. Phytochemical constituents and antileshimanial properties of the leaf latex of A. ghibensis have not been reported. The objective of this study was, therefore, to determine the phytochemical constituents and in vitro antileishmanial activities of the leaf latex of A. ghibensis and its major compounds against two Leishmania species. Preparative TLC was used to isolate compounds from the leaf latex of A. ghibensis and spectroscopic techniques including 1D- and 2D-NMR as well as ESI-MS were employed to elucidate structures of the isolated compounds. In vitro antileishmanial activity was performed against promastigotes and axenically cultured amastigotes of Leishmania aethiopica and Leishmania donovani clinical isolates using Alamar Blue assay. Phytochemical investigation led to the isolation of two major anthrones, identified as aloin A/B and 7-hydroxyaloin A/B. Both the leaf latex of A. ghibensis and isolated compounds showed antileishmanial activity with IC50 values ranging from 1.6 ± 0.43 to 3.64 ± 0.09 µg/ml and 1.87 ± 0.21 to 3.72 ± 0.12 against promastigotes and axenically cultured amastigotes of L. aethopica and L. donovani, respectively. Moreover, the test substances were found to be less toxic (LC50 = 145 ± 0.72 to 156 ± 0.08 µg/ml) than amphotericin B (LC50 = 12.11 ± 0.51 µg/ml) towards human monocytic cell line (THP-1). The present study revealed that the latex and pure compounds possess genuine antileishmanial activity with high selectivity indices (SIs). Therefore, the isolated compounds can be used as a scaffold for the development of effective drugs for leishmaniasis.  

scholarly journals Efficacy of Synthetic Peptides RP-1 and AA-RP-1 against Leishmania SpeciesIn VitroandIn Vivo

2011 ◽  
Vol 56 (2) ◽  
pp. 658-665 ◽  
Author(s):  
Marie Crisel B. Erfe ◽  
Consuelo V. David ◽  
Cher Huang ◽  
Victoria Lu ◽  
Ana Claudia Maretti-Mira ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Synthetic Peptides ◽  
Antileishmanial Activity ◽  
Host Defense Peptides ◽  
Content Type ◽  
Causative Agents ◽  
Antileishmanial Activities ◽  
Conventional Antibiotics

ABSTRACTHost defense peptides are naturally occurring molecules that play essential roles in innate immunity to infection. Based on prior structure-function knowledge, we tested two synthetic peptides (RP-1 and AA-RP-1) modeled on the conserved, microbicidal α-helical domain of mammalian CXCL4 platelet kinocidins. These peptides were evaluated for efficacy againstLeishmaniaspecies, the causative agents of the group of diseases known as leishmaniasis.In vitroantileishmanial activity was assessed against three distinctLeishmaniastrains by measuring proliferation, metabolic activity and parasite viability after exposure to various concentrations of peptides. We demonstrate that micromolar concentrations of RP-1 and AA-RP-1 caused dose-dependent growth inhibition ofLeishmaniapromastigotes. This antileishmanial activity correlated with rapid membrane disruption, as well as with a loss of mitochondrial transmembrane potential. In addition, RP-1 and AA-RP-1 demonstrated distinct and significantin vivoantileishmanial activities in a mouse model of experimental visceral leishmaniasis after intravenous administration. These results establish efficacy of RP-1 lineage synthetic peptides againstLeishmaniaspeciesin vitroand after intravenous administrationin vivoand provide further validation of proof of concept for the development of these and related systemic anti-infective peptides targeting pathogens that are resistant to conventional antibiotics.

scholarly journals Potential Antileishmanial Activity of Essential Oils of Native Species from Southern Brazil

2016 ◽  
Vol 6 (4) ◽  
pp. 18 ◽  
Author(s):  
Carla Kauffmann ◽  
Eduardo M. Ethur ◽  
Barbara Buhl ◽  
Talita Scheibel ◽  
Gerzia M. C. Machado ◽  
...  
Keyword(s):  
Essential Oils ◽  
Native Species ◽  
Neglected Tropical Diseases ◽  
Antileishmanial Activity ◽  
Reference Drug ◽  
Ic50 Values ◽  
Brazilian Flora ◽  
South Of Brazil ◽  
Antileishmanial Activities

Leishmaniasis are a neglected tropical diseases that affecting 98 countries on three continents. Every year, 1.3 million of people are infected with the disease and 50.000 persons die because of this. The aim of this work was to evaluate antileishmanial activities in vitro from native species of South of Brazil belonging to the Myrtaceae family. The essential oils from leaves of Calyptranthes grandifolia, Calyptranthes tricona, Eugenia anomala, Eugenia arenosa, Eugenia pyriformis, Myrrhinium atropurpureum and Psidium salutare were analyzed in vitro for antileishmanial activity against promastigotes of Leishmania amazonensis, employed MTT assay. The essential oils from leaves of C. grandifolia, C. tricona, E. arenosa and E. pyriformis presented IC50 values of 31.27 ± 6.40 µg/mL, 26.13 ± 8.60 µg/mL, 13.72 ± 8.65 µg/mL and 19.73 ± 5.40 µg/mL, respectively, and not are statistically different from pentamidine (IC50 = 23.22 ± 9.04 µg/mL), the reference drug. The results show the potential of essential oils from leaves of C. grandifolia, C. tricona, E. arenosa and E. pyriformis as antileishmanial, as well as the importance of continuing studies to in order to advance in the search and development of new therapeutic options from of brazilian flora sources.

scholarly journals Improvement of In Vitro and In Vivo Antileishmanial Activities of 2′,6′-Dihydroxy-4′-Methoxychalcone by Entrapment in Poly(d,l-Lactide) Nanoparticles

1999 ◽  
Vol 43 (7) ◽  
pp. 1776-1778 ◽  
Author(s):  
Eduardo Caio Torres-Santos ◽  
José M. Rodrigues ◽  
Davyson L. Moreira ◽  
Maria Auxiliadora C. Kaplan ◽  
Bartira Rossi-Bergmann
Keyword(s):  
Polymeric Nanoparticles ◽  
Leishmania Amazonensis ◽  
Antileishmanial Activity ◽  
Antileishmanial Activities ◽  
Piper Aduncum

ABSTRACT The inhibition of intracellular Leishmania amazonensisgrowth by 2′,6′-dihydroxy-4′-methoxychalcone (DMC) isolated fromPiper aduncum was further enhanced after encapsulation of DMC in polymeric nanoparticles. Encapsulated DMC also showed increased antileishmanial activity in infected BALB/c mice, as evidenced by significantly smaller lesions and fewer parasites in the lesions.

Antileishmanial Activity of Carum Copticum Essential Oil Against Leishmania Major [MRHO/IR/75/ER]: An In Vitro Study

2019 ◽  
Author(s):  
Ali Fattahi Bafghi ◽  
Moneyreh Modares Mosadegh ◽  
Mehrdad Ghaemi ◽  
Seyed Hassan Hejazian
Keyword(s):  
Essential Oil ◽  
Leishmania Major ◽  
In Vitro Study ◽  
Antileishmanial Activity ◽  
Control Group ◽  
Synthetic Drugs ◽  
Carum Copticum ◽  
Antileishmanial Activities ◽  
Better Than

Background and Aims: Because of the toxicity and side-effects of synthetic drugs, there is a growing interest in biomedical plants. The aim of this study was to evaluate in vitro antileishmanial activity of Carum copticum essential oil against Leishmania (L) major. Materials and Methods: Nineteen experimental groups were designed to determine the effect of Carum copticum essential oil against L. major and compare it with Meglumine antimonite. Group 1 was the control group and included 200 µl of RPMI 1640 plus 2×105 cells/ml promastigotes. Groups 2-10 included the aforementioned substances plus 10 µl of 0.01, 0.02, 0.05, 0.1, 0.2, 0.5, 1, 2 and 3 µg/ml of Carum copticum essential oil respectively. Groups 11-19 were similar to groups 2-10 but Meglumine antimonite (0.01, 0.02, 0.05, 0.1, 0.2, 0.5, 1, 2 and 3 µg/ml) was used instead of Carum copticum essential oil. All the experiments were repeated five times. After 8 hours, the antileishmanial activities of studied substances were determined. Results: Up to concentration of 0.5 µg/ml, no effect was observed with both substances. In comparison to control group, at 1 and 2 µg/ml, Meglumine antimonite had no effect on Leishmaniasis (p>0.05) while Carum copticum essential oil significantly decreased Leishmaniasis viability (p<0.05). Moreover, at 3 µg/ml, both compounds significantly decreased Leishmaniasis viability (p<0.05). However, Carum copticum essential oil had substantially better Antileishmanial activity than the other.   Conclusions: These results suggest that comparable concentrations, in vitro antileishmanial activity of Carum copticum essential oil is better than Meglumine antimonite.

scholarly journals Antileishmanial Activities of Stearylamine-Bearing Liposomes

2000 ◽  
Vol 44 (6) ◽  
pp. 1739-1742 ◽  
Author(s):  
Tuhina Dey ◽  
Khairul Anam ◽  
Farhat Afrin ◽  
Nahid Ali
Keyword(s):  
Single Dose ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Therapeutic Potential ◽  
Parasite Burden ◽  
Intracellular Amastigotes ◽  
Antileishmanial Activities

ABSTRACT Here we report the activity of liposomes comprising egg phosphatidylcholine (PC) and stearylamine (SA) against Leishmania donovani parasites. Both promastigotes and intracellular amastigotes in vitro and in vivo were susceptible to SA-PC liposomes. A single dose of 55 mg of SA-PC liposomes/animal could significantly reduce the hepatic parasite burden by 85 and 68% against recent and established experimental visceral leishmaniasis, respectively, suggesting their strong therapeutic potential.

Derivatives of 5-Aminolevulinic Acid for Photodynamic Therapy

2007 ◽  
Vol 1 ◽  
pp. 1177391X0700100 ◽  
Author(s):  
Ryan F. Donnelly ◽  
Paul A. McCarron ◽  
David A. Woolfson
Keyword(s):  
Photodynamic Therapy ◽  
Side Effects ◽  
Aminolevulinic Acid ◽  
Skin Lesions ◽  
Rational Approach ◽  
Topical Formulation ◽  
Systemic Bioavailability ◽  
Clinical Benefits ◽  
Derivatives Of

Photodynamic therapy (PDT) is a clinical treatment that combines the effects of visible light irradiation with subsequent biochemical events that arise from the presence of a photosensitising drug (possessing no dark toxicity) to cause destruction of selected cells. Today, the most common agent used in dermatological PDT is 5-aminolevulinic acid (ALA). As a result of its hydrophilic character, ALA penetrates skin lesions poorly when applied topically. Its systemic bioavailability is limited and it is known to cause significant side effects when given orally or intravenously. Numerous chemical derivatives of ALA have been synthesised with the aims of either improving topical penetration or enhancing systemic bioavailability, while reducing side effects. In vitro cell culture experiments with ALA derivatives have yielded promising results. However, if ALA derivatives are to demonstrate meaningful clinical benefits, a rational approach to topical formulation design is required, along with a systematic study aimed at uncovering the true potential of ALA derivatives in photodynamic therapy. With respect to systemic ALA delivery, more study is required in the developing area of ALA-containing dendrons and dendrimers.

scholarly journals Evaluation of theIn VitroAntiplasmodial, Antileishmanial, and Antitrypanosomal Activity of Medicinal Plants Used in Saudi and Yemeni Traditional Medicine

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ramzi A. Mothana ◽  
Nawal M. Al-Musayeib ◽  
Mohamed F. Al-Ajmi ◽  
Paul Cos ◽  
Louis Maes
Keyword(s):  
Medicinal Plants ◽  
High Selectivity ◽  
Moderate Activity ◽  
Good Activity ◽  
Antiprotozoal Activity ◽  
Traditional Use ◽  
Active Constituents ◽  
Intracellular Amastigotes ◽  
Antitrypanosomal Activity

The antiplasmodial, antileishmanial, and antitrypanosomal activity of twenty-five medicinal plants distributed in Saudi Arabia and Yemen was evaluated. The plants were extracted with methanol and screenedin vitroagainst erythrocytic schizonts ofPlasmodium falciparum, intracellular amastigotes ofLeishmania infantumandTrypanosoma cruzi, and free trypomastigotes ofT. brucei. To assess selectivity, cytotoxicity was determined on MRC-5 cells. Criteria for activity were anIC50<10 μg/mL and high selectivity (SI). Seven plants showed interesting antiprotozoal activity in one or more models. Extracts ofCaralluma penicillataandAcalypha ciliatashowed fairly good activity againstP. falciparumwith IC50of 6.7 and 10.8 μg/mL and adequate selectivity (SI>9.6and>5.9). Interesting activity againstL. infantumwas obtained withVerbascum bottae(IC50of 3.2 μg/mL, SI 10.2) andSolanum glabratum(IC508.1 μg/mL, SI 3.4). The extracts ofC. penicillata, Leucas virgata, Loranthus regularis, andV. bottaeexhibited moderate activity againstT. brucei(IC508.5, 8.1, 8.3, and 2.3 μg/mL;SI>7.6, 7.7, 4.3, and>14.1). These results partly support the traditional use of some of the selected medicinal plants and warrant further investigations into the putative active constituents.

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