scholarly journals Review 2: Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase

2020 ◽  
Author(s):  
Marta Branquinha
Keyword(s):  
Leishmania Donovani ◽  
Computational Approach ◽  
Squalene Synthase ◽  
Antileishmanial Activity

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.

scholarly journals Antileishmanial Activities of Several Classes of Aromatic Dications

2002 ◽  
Vol 46 (3) ◽  
pp. 797-807 ◽  
Author(s):  
James J. Brendle ◽  
Abram Outlaw ◽  
Arvind Kumar ◽  
David W. Boykin ◽  
Donald A. Patrick ◽  
...  
Keyword(s):  
Cell Line ◽  
Leishmania Donovani ◽  
Pneumocystis Carinii ◽  
Antileishmanial Activity ◽  
Microbial Pathogens ◽  
Mouse Macrophage ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Mouse Macrophage Cell Line

ABSTRACT Aromatic dicationic molecules possess impressive activity against a broad spectrum of microbial pathogens, including Pneumocystis carinii, Cryptosporidium parvum, and Candida albicans. In this work, 58 aromatic cations were examined for inhibitory activity against axenic amastigote-like Leishmania donovani parasites. In general, the most potent of the compounds were substituted diphenyl furan and thiophene dications. 2,5-Bis-(4-amidinophenyl)thiophene was the most active compound. This agent displayed a 50% inhibitory concentration (IC50) of 0.42 ± 0.08 μM against L. donovani and an in vitro antileishmanial potency 6.2-fold greater than that of the clinical antileishmanial dication pentamidine and was 155-fold more toxic to the parasites than to a mouse macrophage cell line. 2,4-Bis-(4-amidinopheny)furan was twice as active as pentamidine (IC50, 1.30 ± 0.21 μM), while 2,5-bis-(4-amidinopheny)furan and pentamidine were essentially equipotent in our in vitro antileishmanial assay. Carbazoles, dibenzofurans, dibenzothiophenes, and benzimidazoles containing amidine or substituted amidine groups were generally less active than the diphenyl furans and thiophenes. In all cases, aromatic dications possessing strong antileishmanial activity were severalfold more toxic to the parasites than to a cultured mouse macrophage cell line. These structure-activity relationships demonstrate the potent antileishmanial activity of several aromatic dications and provide valuable information for the future design and synthesis of more potent antiparasitic agents.

scholarly journals Recombinant human granulocyte/macrophage colony-stimulating factor activates intracellular killing of Leishmania donovani by human monocyte-derived macrophages.

1987 ◽  
Vol 166 (5) ◽  
pp. 1436-1446 ◽  
Author(s):  
W Y Weiser ◽  
A Van Niel ◽  
S C Clark ◽  
J R David ◽  
H G Remold
Keyword(s):  
Leishmania Donovani ◽  
Human Monocyte ◽  
Peripheral Blood Monocyte ◽  
Antileishmanial Activity ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) obtained from cloned complementary Mo cell DNA and expressed in COS-1 cells activates cultured peripheral blood monocyte-derived macrophages in vitro to become cytotoxic for intracellular L. donovani. The antileishmanial effect of rGM-CSF, which can be completely neutralized by anti-rGM-CSF antiserum, is maximal after 36 h preincubation with the cultured macrophages, compared with that of rIFN-gamma, which reaches its maximum at 72 h of preincubation. The antileishmanial effect of GM-CSF as well as IFN-gamma is independent of detectable amounts of LPS and is not augmented by the addition of 10 or 50 ng/ml of LPS. Simultaneous administration of suboptimal doses of rGM-CSF and rIFN-gamma to monocyte-derived macrophages results in greater antileishmanial activity by these cells than administration of either lymphokine alone, although no enhancement of antileishmanial activity is observed when optimal doses of these two lymphokines are applied together.

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 Cloning, overexpression and characterization of Leishmania donovani squalene synthase

2010 ◽  
Vol 311 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Prachi Bhargava ◽  
Kishore Kumar ◽  
Shailendra S. Chaudhaery ◽  
Anil K. Saxena ◽  
Uma Roy
Keyword(s):  
Leishmania Donovani ◽  
Squalene Synthase
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