scholarly journals Resveratrol analogues present effective antileishmanial activity against promastigotes and amastigotes from distinct Leishmania species by multitarget action in the parasites

2019 ◽  
Vol 71 (12) ◽  
pp. 1854-1863 ◽  
Author(s):  
Luciana Maria Ribeiro Antinarelli ◽  
Raissa Soares Meinel ◽  
Eduardo Antonio Ferraz Coelho ◽  
Adilson David Silva ◽  
Elaine Soares Coimbra
Keyword(s):  
Leishmania Species ◽  
Antileishmanial Activity ◽  
Resveratrol Analogues

scholarly journals Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes

2021 ◽  
Vol 17 ◽  
Author(s):  
Thiago M. de Aquino ◽  
Paulo H. B. França ◽  
Érica E. E. S. Rodrigues ◽  
Igor J. S. Nascimento ◽  
Paulo F. S. Santos-Júnior ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Leishmania Species ◽  
Antileishmanial Activity ◽  
Trypanothione Reductase ◽  
Aromatic Substituent ◽  
In Silico Studies ◽  
Ic50 Values ◽  
The Impact

Background: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. Objective: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds. Method: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software. Result: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. Conclusion: The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

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.  

Evaluation of the in vitro and in vivo antileishmanial activity of a chloroquinolin derivative against Leishmania species capable of causing tegumentary and visceral leishmaniasis

2019 ◽  
Vol 199 ◽  
pp. 30-37 ◽  
Author(s):  
Tauane G. Soyer ◽  
Débora V.C. Mendonça ◽  
Grasiele S.V. Tavares ◽  
Daniela P. Lage ◽  
Daniel S. Dias ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Species ◽  
Antileishmanial Activity

scholarly journals In Vitro and In Silico Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel Streptomyces smyrnaeus Strain UKAQ_23

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 887
Author(s):  
Kamal A. Qureshi ◽  
Ibrahim Al Nasr ◽  
Waleed S. Koko ◽  
Tariq A. Khan ◽  
M. Qaiser Fatmi ◽  
...  
Keyword(s):  
In Silico ◽  
Leishmania Major ◽  
Actinomycin D ◽  
Leishmania Species ◽  
Binding Pocket ◽  
Docking Studies ◽  
Antileishmanial Activity ◽  
Target Protein ◽  
Lutzomyia Longipalpis

Leishmaniasis, a Neglected Tropical Parasitic Disease (NTPD), is induced by several Leishmania species and is disseminated through sandfly (Lutzomyia longipalpis) bites. The parasite has developed resistance to currently prescribed antileishmanial drugs, and it has become pertinent to the search for new antileishmanial agents. The current study aimed to investigate the in vitro and in silico antileishmanial activity of two newly sourced actinomycins, X2 and D, produced by the novel Streptomyces smyrnaeus strain UKAQ_23. The antileishmanial activity conducted on promastigotes and amastigotes of Leishmania major showed actinomycin X2 having half-maximal effective concentrations (EC50), at 2.10 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and selectivity index (SI) values of 0.048 and 1, respectively, while the actinomycin D exhibited EC50 at 1.90 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and SI values of 0.052 and 1. The molecular docking studies demonstrated squalene synthase as the most favorable antileishmanial target protein for both the actinomycins X2 and D, while the xanthine phosphoribosyltransferase was the least favorable target protein. The molecular dynamics simulations confirmed that both the actinomycins remained stable in the binding pocket during the simulations. Furthermore, the MMPBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) binding energy calculations established that the actinomycin X2 is a better binder than the actinomycin D. In conclusion, both actinomycins X2 and D from Streptomyces smyrnaeus strain UKAQ_23 are promising antileishmanial drug candidates and have strong potential to be used for treating the currently drug-resistant leishmaniasis.

scholarly journals Synthesis and Antileishmanial Activity of Lipophilic Aromatic Aminoalcohols

2010 ◽  
Vol 10 ◽  
pp. 1067-1072 ◽  
Author(s):  
Roberta Novaes Reis Corrales ◽  
Liliane Sena Pinheiro ◽  
Elaine Soares Coimbra ◽  
Adilson David Da Silva ◽  
Mireille Le Hyaric
Keyword(s):  
Antiproliferative Activity ◽  
Leishmania Species ◽  
Antileishmanial Activity ◽  
Good Activity ◽  
Preparation And Evaluation

In this work, we report on the preparation and evaluation of thein vitroantileishmanial activity of a series of lipophilic aromatic aminoalcohols. All compounds were assessed for theirin vitroactivity against promastigotes of threeLeishmania speciesThe most lipophilic aminoalcohols bearing an aliphatic moiety with eight to 12 carbon atoms displayed a good activity againstL. amazonensisandL. major, and two of them also showed antiproliferative activity againstL. chagasi. The best results were obtained for the N-dodecanoyl ethylenediamine derivative and for N-decyl aminoalcohol (IC50= 5.2 and 0.7μM, respectively).

scholarly journals Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase

2020 ◽  
Vol 1 ◽  
Author(s):  
Padmika Wadanambi
Keyword(s):  
Leishmania Donovani ◽  
Neglected Tropical Diseases ◽  
Homology Model ◽  
Leishmania Species ◽  
Vital Role ◽  
Squalene Synthase ◽  
Antileishmanial Activity ◽  
Causative Agents ◽  
Parasite Viability ◽  
Ucsf Chimera

AbstractLeishmania species are the causative agents for Leishmaniasis which is one of the neglected tropical diseases causing 70,000 deaths worldwide each year. Squalene synthase enzyme plays a vital role in sterol metabolism which is essential for Leishmania parasite viability. Therefore squalene synthase of Leishmania donovani is a therapeutic target to inhibit growth of parasite. The 3D model of Leishmania donovani Squalene Synthase (LdSQS) was generated by homology modeling and validated through PROCHECK, ERRAT, VERIFY3D and PROSA tools. Virtual screening of the protein was performed by AutoDock with reported inhibitor, E5700 and two natural alkaloids. Molecular interactions were explored to understand the nature of intermolecular bonds between active ligand and the protein binding site residues using UCSF Chimera and PLIP server. The reported inhibitor showed the best binding affinity (-9.75 kcal/mol) closely followed by Ancistrotanzanine B (-9.55 kcal/mol) and Holamine (-8.79 kcal/mol). Ancistrotanzanine B showed low binding energy and permissible ADMET properties. Based on the present study, homology model of LdSQS and Ancistrotanzanine B can be used to design inhibitors with antileishmanial activity.

A chloroquinoline derivate presents effective in vitro and in vivo antileishmanial activity against Leishmania species that cause tegumentary and visceral leishmaniasis

2019 ◽  
Vol 73 ◽  
pp. 101966 ◽  
Author(s):  
Jessica K.T. Sousa ◽  
Luciana M.R. Antinarelli ◽  
Débora V.C. Mendonça ◽  
Daniela P. Lage ◽  
Grasiele S.V. Tavares ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Species ◽  
Antileishmanial Activity

An effective in vitro and in vivo antileishmanial activity and mechanism of action of 8-hydroxyquinoline against Leishmania species causing visceral and tegumentary leishmaniasis

2016 ◽  
Vol 217 ◽  
pp. 81-88 ◽  
Author(s):  
Mariana Costa Duarte ◽  
Letícia Martins dos Reis Lage ◽  
Daniela Pagliara Lage ◽  
Juliana Tonini Mesquita ◽  
Beatriz Cristina Silveira Salles ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Leishmania Species ◽  
Antileishmanial Activity ◽  
Tegumentary Leishmaniasis

A Systematic Literature Review of Curcumin With Promising Antileishmanial Activity

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Saberi ◽  
Mahdi Fakhar ◽  
Shabnam Asfaram ◽  
Javad Akhtari ◽  
Maryam Nakhaei ◽  
...  
Keyword(s):  
Systematic Review ◽  
Literature Review ◽  
Bioactive Compounds ◽  
Leishmania Species ◽  
Inhibitory Effect ◽  
Antileishmanial Activity ◽  
Eligibility Criteria ◽  
Intracellular Amastigote ◽  
Leishmania Parasites

Background: Curcumin (CUR) is a bright yellow chemical and it is used as an additive in foods. Recently CUR and its associated bioactive compounds have received much attention in the literature review. The aim of this systematic review is to overview antileishmanial properties of CUR and its mechanism, perhaps the results of this study will be used for therapeutic and preventive purposes. Methods: Following the PRISMA guidelines, international databases were systematically searched for studies published until September 2019. Articles related to the subject were selected and included in this systematic review. Results: A total of 15 articles met our eligibility criteria. Then, the effect of CUR and its associated bioactive compounds on Leishmania species was evaluated. In most studies CUR/derivatives were tested on L. major and in vitro condition. Most investigations were conducted on the promastigote rather than the more relevant intracellular amastigote stage. Our results showed that CUR overcomes the inhibitory effect of nitric oxide (NO) on Leishmania parasites. Conclusions: This review indicated that CUR derivatives instead of alone CUR showed a high potential to serve as an effective herbal drug against leishmaniasis. Moreover, we concluded that the antileishmanial activity of CUR/bioactive compounds is mostly due to increasing oxidative stress and inducing apoptosis.

scholarly journals Antileishmanial activity of sulphonamide nanoemulsions targeting the β-carbonic anhydrase from Leishmania species

2018 ◽  
Vol 33 (1) ◽  
pp. 850-857 ◽  
Author(s):  
Verônica da Silva Cardoso ◽  
Alane Beatriz Vermelho ◽  
Eduardo Ricci Junior ◽  
Igor Almeida Rodrigues ◽  
Ana Maria Mazotto ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Leishmania Species ◽  
Antileishmanial Activity
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