scholarly journals IN VITRO ANTILEISHMANIAL ACTIVITIES OF THREE MEDICINAL PLANTS: ARGEMONE MEXICANA, MURRAYA KOENIGII AND CINNAMOMUM TAMALA AGAINST MILTEFOSINE RESISTANT PROMASTIGOTES OF LEISHMANIA DONOVANI PARASITES

2021 ◽  
pp. 27-33
Author(s):  
SIRIN SALMA SULTANA
Keyword(s):  
Medicinal Plants ◽  
Leishmania Donovani ◽  
Neglected Tropical Diseases ◽  
Protein Biosynthesis ◽  
New Drugs ◽  
Murraya Koenigii ◽  
Argemone Mexicana ◽  
Cinnamomum Tamala ◽  
Antileishmanial Activities

Objective: Leishmaniasis is one of the neglected tropical diseases in terms of drug development and discovery. Non-responsiveness and resistance to the drug in Leishmania species need to develop new antileishmanial potentials; herbal medicines could be the alternative one. Methods: In the present study, semi-purified fractions were prepared from the traditionally used three medicinal plants of India: Argemone mexicana (aerial shoot), Murraya koenigii (stem), and Cinnamomum tamala (bark) by using multiple solvent systems (non-polar to polar, beginning with petroleum ether followed by n-hexane, benzene, and chloroform) and an effort was given to assess the leishmanicidal activities against Leishmania donovani miltefosine resistant HePC-R (Ld/MIL-30) promastigotes in vitro and the IC50 concentrations were estimated. Results: The study revealed that the semi-purified fractions of A. mexicana, M. koenigii, and C. tamala have effective antileishmanial activities and the 50% inhibitory concentrations (IC50) are 50 μg/ml, 98 μg/ml, and 200 μg/ml, respectively. At these (IC50) concentrations, these plant semi-purified fractions were found to interfere in lipid and protein biosynthesis, alter cell morphology, DNA content, mitochondrial membrane potential, generating ROS, and apoptosis in promastigotes. The semi-purified fractions were also found noticeably non-toxic towards host splenocytes. Conclusion: These results could suggest that A. mexicana, M. koenigii, and C. tamala could carry potential novel compounds for the development of new drugs against Leishmaniasis.

The Role of nitro (NO2-), chloro (Cl), and fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds

2020 ◽  
Vol 21 ◽  
Author(s):  
Boniface Pone ◽  
Ferreira Igne Elizabeth
Keyword(s):  
Chagas Disease ◽  
Mammalian Cells ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Pharmacokinetic Studies ◽  
Scientific Publications ◽  
Antitrypanosomal Activity ◽  
Chemical Groups

: Neglected tropical diseases (NTDs) are responsible for over 500,000 deaths annually and are characterized by multiple disabilities. Leishmaniasis and Chagas disease are among the most severe NTDs, and are caused by the Leishmania sp, and Trypanosoma cruzi, respectively. Glucantime, pentamidine and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease. However, these treatments are associated with drug resistance, and severe side effects. Hence, the development of synthetic products, especially those containing N02, F, or Cl, which chemical groups are known to improve the biological activity. The present work summarizes the information on the antileishmanial and antitrypanosomal activity of nitro-, chloro-, and fluoro-synthetic derivatives. Scientific publications referring to halogenated derivatives in relation to antileishmanial and antitrypanosomal activities were hand searched in databases such as SciFinder, Wiley, Science Direct, PubMed, ACS, Springer, Scielo, and so on. According to the literature information, more than 90 compounds were predicted as lead molecules with reference to their IC50/EC50 values in in vitro studies. It is worth to mention that only active compounds with known cytotoxic effects against mammalian cells were considered in the present study. The observed activity was attributed to the presence of nitro-, fluoro- and chloro-groups in the compound backbone. All in all, nitro and h0alogenated derivatives are active antileishmanial and antitrypanosomal compounds and can serve as baseline for the development of new drugs against leishmaniasis and Chagas disease. However, efforts on in vitro and in vivo toxicity studies of the active synthetic compounds is still needed. Pharmacokinetic studies, and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity.

scholarly journals Design, Synthesis and Antiparasitic Evaluation of Click Phospholipids

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4204
Author(s):  
George E. Magoulas ◽  
Pantelis Afroudakis ◽  
Kalliopi Georgikopoulou ◽  
Marina Roussaki ◽  
Chiara Borsari ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Developmental Stages ◽  
Neglected Tropical Diseases ◽  
Heterocyclic Ring ◽  
Head Group ◽  
Ether Phospholipid ◽  
Design Synthesis ◽  
Antiparasitic Activity ◽  
Intracellular Amastigotes

A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure–activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 μM. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases.

scholarly journals Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro.

2000 ◽  
Vol 47 (1) ◽  
pp. 113-120 ◽  
Author(s):  
K Bielawski ◽  
A Galicka ◽  
A Bielawska ◽  
K Sredzińska
Keyword(s):  
Protein Biosynthesis ◽  
Elongation Factor ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Clinical Use ◽  
Inhibitory Effects ◽  
Inhibit Protein Synthesis ◽  
Primary Target ◽  
Eukaryotic Elongation Factor

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds differed in the precise mode of action. The inhibitory effect of I on the activity of the eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the binding site of eEF-2 on the ribosome was blocked by this compound. eEF-2 has been identified as the primary target of II and eEF-1 as the primary target of DAPI in the system studied.

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 Susceptibility Testing of Medically Important Parasites

2017 ◽  
Vol 30 (3) ◽  
pp. 647-669 ◽  
Author(s):  
Abebe Genetu Bayih ◽  
Anjan Debnath ◽  
Edward Mitre ◽  
Christopher D. Huston ◽  
Benoît Laleu ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Neglected Tropical Diseases ◽  
State Of The Art ◽  
Life Cycles ◽  
Point Of View ◽  
New Drugs ◽  
Screening Methods ◽  
Laboratory Methods ◽  
Antiparasitic Agents

SUMMARY In the last 2 decades, renewed attention to neglected tropical diseases (NTDs) has spurred the development of antiparasitic agents, especially in light of emerging drug resistance. The need for new drugs has required in vitro screening methods using parasite culture. Furthermore, clinical laboratories sought to correlate in vitro susceptibility methods with treatment outcomes, most notably with malaria. Parasites with their various life cycles present greater complexity than bacteria, for which standardized susceptibility methods exist. This review catalogs the state-of-the-art methodologies used to evaluate the effects of drugs on key human parasites from the point of view of drug discovery as well as the need for laboratory methods that correlate with clinical outcomes.

scholarly journals Anti-malarial drugs as potential inhibitors of leishmania glycolytic enzymes: Development of new anti-leishmanial agents

2020 ◽  
Vol 5 (3) ◽  
pp. 77
Author(s):  
Bashir Alsiddig Yousef ◽  
Tanzeel Haider Elwaseela ◽  
Tagwa Abdalla Ali ◽  
Fatima Elamin Mohammed ◽  
Wala Osman Mohammed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Leishmania Donovani ◽  
Triosephosphate Isomerase ◽  
Antimalarial Drugs ◽  
Binding Energies ◽  
Glycolytic Enzymes ◽  
Glycolytic Pathway ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Antileishmanial Activities

Leishmaniasis is one of the most important endemic diseases in Sudan. The glycolytic pathway is one of the essential pathways in the survival and pathogenicity of the leishmania parasite. This study aimed to evaluate the antileishmanial activities of three antimalarial drugs through targeting the glycolytic pathway inside the parasite. Antileishmanial activities of artesunate, quinine and mefloquine were evaluated using an in vitro anti-promastigote assay. Then, in silico molecular docking was conducted using Autodock 4.0 software to study the molecular interactions of antimalarial drugs to different key glycolytic enzymes. The results of the current study, Artesunate, quinine, and mefloquine showed effective inhibitory activities against L. donovani with IC50 values of 58.85, 40.24, and 20.06 μg/ml, respectively. Molecular docking analysis revealed interesting interactions between different antimalarial drugs and various glycolytic enzymes (Glucose-6-phosphate isomerase, Triosephosphate isomerase, Glycerol-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase and Pyruvate kinase). Moreover, these drugs interact with different amino acid residues of the proteins with satisfactory binding energies, particularly with artesunate. According to binding energies, Glycerol-3-phosphate dehydrogenase was represented the most potential target for three tested drugs. Collectively, our results showed promising antileishmanial activities of different antimalarial that may mediated through inhibition of glycolysis process in leishmania donovani promastigote.

In vitro antiplasmodial, antitrypanosomal and antileishmanial activities of selected medicinal plants from Ugandan flora: Refocusing into multi-component potentials

2019 ◽  
Vol 229 ◽  
pp. 127-136 ◽  
Author(s):  
C.J.D. Obbo ◽  
S.T. Kariuki ◽  
J.W. Gathirwa ◽  
W. Olaho-Mukani ◽  
P.K. Cheplogoi ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Antileishmanial Activities

scholarly journals Repurposing Auranofin and Evaluation of a New Gold(I) Compound for the Search of Treatment of Human and Cattle Parasitic Diseases: From Protozoa to Helminth Infections

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5075
Author(s):  
Liwen Feng ◽  
Sébastien Pomel ◽  
Perle Latre de Late ◽  
Alexandre Taravaud ◽  
Philippe M. Loiseau ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Reductase Activity ◽  
Thioredoxin Reductase ◽  
New Drugs ◽  
Public Health Issue ◽  
Parasitic Diseases ◽  
Irreversible Inhibitor ◽  
Helminth Infections ◽  
Thioredoxin Reductases

Neglected parasitic diseases remain a major public health issue worldwide, especially in tropical and subtropical areas. Human parasite diversity is very large, ranging from protozoa to worms. In most cases, more effective and new drugs are urgently needed. Previous studies indicated that the gold(I) drug auranofin (Ridaura®) is effective against several parasites. Among new gold(I) complexes, the phosphole-containing gold(I) complex {1-phenyl-2,5-di(2-pyridyl)phosphole}AuCl (abbreviated as GoPI) is an irreversible inhibitor of both purified human glutathione and thioredoxin reductases. GoPI-sugar is a novel 1-thio-β-d-glucopyranose 2,3,4,6-tetraacetato-S-derivative that is a chimera of the structures of GoPI and auranofin, designed to improve stability and bioavailability of GoPI. These metal-ligand complexes are of particular interest because of their combined abilities to irreversibly target the essential dithiol/selenol catalytic pair of selenium-dependent thioredoxin reductase activity, and to kill cells from breast and brain tumors. In this work, screening of various parasites—protozoans, trematodes, and nematodes—was undertaken to determine the in vitro killing activity of GoPI-sugar compared to auranofin. GoPI-sugar was found to efficiently kill intramacrophagic Leishmania donovani amastigotes and adult filarial and trematode worms.

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.

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