Antileishmanial Activity of Diterpene lactones from Suregada multiflora and Their Semisynthetic Derivatives

2020 ◽  
Vol 16 (1) ◽  
pp. 53-57
Author(s):  
Humaira Y. Gondal ◽  
Muhammad Nisar ◽  
Muhammad I. Choudhary
Keyword(s):  
Brine Shrimp ◽  
Low Cost ◽  
Alternative Therapy ◽  
Protozoan Parasite ◽  
Structural Diversity ◽  
Chemotherapeutic Agents ◽  
Antileishmanial Activity ◽  
Cytotoxic Effects ◽  
Ic50 Values

Background: There is a general lack of effective and economical chemotherapeutic agents for the treatment of widely prevalent leishmanias. To develop locally available, low cost alternative therapy, a series of diterpene lactones isolated from Suregada multiflora and their semisynthetic derivatives have been evaluated against the protozoan parasite Leishmania. Methods: A series of diterpene lactones were isolated from methanolic extract of Suregada multiflora. Major constituents were further derivatized through chemical and microbial transformations. Antileishmanial activity of structurally diverse diterpene lactones was performed by testing them in vitro against L. donovani promastigotes. All compounds were also tested for their cytotoxic effects by the brine shrimp bioassay. Results: Among all compounds evaluated in current studies, natural diterpenes Gelomulide A (1) and G (2) were found significantly active with IC50 values below 20µg/ml. While, among synthesized derivatives; compounds 5, 9 and 10 were found more potent with IC50 value 17.49, 18.38 and 17.81µg/ml, respectively. None of these compounds showed cytotoxic effects in the brine shrimp bioassay (LC50> 300). Conclusion: A new class of diterpene lactones was identified as potential antileshmanial agent. The structural diversity of natural and semisynthetic diterpene lactones, helped to rationalize structure– activity relationships. Activity of these diterpene lactones owed to C-8/14 epoxide along with unsubstituted C-1. Keto group at C-1 always lower the activity unless it is in α, β-unsaturated form. Presence of acetyl group at C-3 and 6 usually augmented the antileishmanila potential

scholarly journals Characterization and selective inhibition of myristoyl-CoA:protein N-myristoyltransferase from Trypanosoma brucei and Leishmania major

2006 ◽  
Vol 396 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Chrysoula Panethymitaki ◽  
Paul W. Bowyer ◽  
Helen P. Price ◽  
Robin J. Leatherbarrow ◽  
Katherine A. Brown ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Leishmania Major ◽  
Homo Sapiens ◽  
Selective Inhibition ◽  
Fungal Species ◽  
Chemotherapeutic Agents ◽  
Human Pathogens ◽  
Ic50 Values

The eukaryotic enzyme NMT (myristoyl-CoA:protein N-myristoyltransferase) has been characterized in a range of species from Saccharomyces cerevisiae to Homo sapiens. NMT is essential for viability in a number of human pathogens, including the fungi Candida albicans and Cryptococcus neoformans, and the parasitic protozoa Leishmania major and Trypanosoma brucei. We have purified the Leishmania and T. brucei NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and specific peptide substrates. A number of inhibitory compounds that target NMT in fungal species have been tested against the parasite enzymes in vitro and against live parasites in vivo. Two of these compounds inhibit TbNMT with IC50 values of <1 μM and are also active against mammalian parasite stages, with ED50 (the effective dose that allows 50% cell growth) values of 16–66 μM and low toxicity to murine macrophages. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against infectious diseases including African sleeping sickness and Nagana.

scholarly journals In vivo and in vitro antiplasmodial activities of some plants traditionally used in Guatemala against malaria.

1997 ◽  
Vol 41 (7) ◽  
pp. 1500-1503 ◽  
Author(s):  
F F Franssen ◽  
L J Smeijsters ◽  
I Berger ◽  
B E Medinilla Aldana
Keyword(s):  
Plasmodium Berghei ◽  
Brine Shrimp ◽  
Folk Medicine ◽  
Artemia Salina ◽  
In Vitro Cultures ◽  
Cytotoxic Effects ◽  
Resistant Strains ◽  
Simarouba Glauca

We present an evaluation of the antiplasmodial and cytotoxic effects of four plants commonly used in Guatemalan folk medicine against malaria. Methanol extracts of Simarouba glauca D. C., Sansevieria guineensis Willd, Croton guatemalensis Lotsy, and Neurolaena lobata (L.)R.Br. significantly reduced parasitemias in Plasmodium berghei-infected mice. Dichloromethane fractions were screened for their cytotoxicities on Artemia salina (brine shrimp) larvae, and 50% inhibitory concentrations were determined for Plasmodium falciparum in in vitro cultures. Both chloroquine-susceptible and -resistant strains of P. falciparum were significantly inhibited by these extracts. Of all dichloromethane extracts, only the S. glauca cortex extract was considered to be toxic to nauplii of A. salina in the brine shrimp test.

Enhancement of Cytotoxic Effects of Chemotherapeutic Agents with Hyperthermia In Vitro

2001 ◽  
pp. 451-455 ◽  
Author(s):  
Toshio Ohtsubo ◽  
Eiichi Kano ◽  
Sachiko Hayashi ◽  
Masanori Hatashita ◽  
Hideki Matsumoto ◽  
...  
Keyword(s):  
Chemotherapeutic Agents ◽  
Cytotoxic Effects

scholarly journals Trifluoromethionine, a Prodrug Designed against Methionine γ-Lyase-Containing Pathogens, Has Efficacy In Vitro and In Vivo against Trichomonas vaginalis

2001 ◽  
Vol 45 (6) ◽  
pp. 1743-1745 ◽  
Author(s):  
Graham H. Coombs ◽  
Jeremy C. Mottram
Keyword(s):  
Drug Target ◽  
Trichomonas Vaginalis ◽  
Anaerobic Bacteria ◽  
Protozoan Parasite ◽  
Chemotherapeutic Agents ◽  
Single Step ◽  
Lesion Formation ◽  
Highly Active

ABSTRACT Methionine γ-lyase, the enzyme which catalyzes the single-step conversion of methionine to α-ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploited as a drug target by prodrugs that are exclusively activated by it. Trifluoromethionine was confirmed as such a prodrug and shown to be highly toxic in vitro to the anaerobic protozoan parasiteTrichomonas vaginalis, to anaerobic bacteria containing methionine γ-lyase, and to Escherichia coli expressing the trichomonad gene. The compound also has exceptional activity against the parasite growing in vivo, with a single dose preventing lesion formation in five of the six mice challenged. These findings suggest that trifluoromethionine represents a lead compound for a novel class of anti-infective drugs with potential as chemotherapeutic agents against a range of prokaryotic and eukaryotic anaerobic pathogens.

scholarly journals Novel Arsenic Nanoparticles Are More Effective and Less Toxic than As (III) to Inhibit Extracellular and Intracellular Proliferation ofLeishmania donovani

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Sudipta Chakraborty ◽  
Kaushik Bhar ◽  
Sandip Saha ◽  
Rajarshi Chakrabarti ◽  
Anjali Pal ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Antileishmanial Activity ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Vector Borne ◽  
First Time ◽  
Intracellular Proliferation ◽  
Mouse Macrophage Cell Line

Visceral leishmaniasis, a vector-borne tropical disease that is threatening about 350 million people worldwide, is caused by the protozoan parasiteLeishmania donovani. Metalloids like arsenic and antimony have been used to treat diseases like leishmaniasis caused by the kinetoplastid parasites. Arsenic (III) at a relatively higher concentration (30 μg/mL) has been shown to have antileishmanial activity, but this concentration is reported to be toxic in several experimental mammalian systems. Nanosized metal (0) particles have been shown to be more effective than their higher oxidation state forms. There is no information so far regarding arsenic nanoparticles (As-NPs) as an antileishmanial agent. We have tested the antileishmanial properties of the As-NPs, developed for the first time in our laboratory. As-NPs inhibited thein vitrogrowth, oxygen consumption, infectivity, and intramacrophage proliferation ofL. donovaniparasites at a concentration which is about several fold lower than that of As (III). Moreover, this antileishmanial activity has comparatively less cytotoxic effect on the mouse macrophage cell line. It is evident from our findings that As-NPs have more potential than As (III) to be used as an antileishmanial agent.

scholarly journals Ethanolic extract of gabirobeira (Campomanesia adamantium) leaves reduces proliferation of osteosarcoma cells in vitro

2021 ◽  
Vol 43 ◽  
pp. e52783
Author(s):  
Nara Cristina Silva ◽  
Leandro Lopes Nepomuceno ◽  
Nayane Peixoto Soares ◽  
Vanessa de Souza Vieira ◽  
Vanessa de Sousa Cruz ◽  
...  
Keyword(s):  
Ethanolic Extract ◽  
Metastatic Potential ◽  
Chemotherapeutic Agents ◽  
In Vitro Cytotoxicity ◽  
Osteosarcoma Cells ◽  
Trypan Blue Exclusion ◽  
Trypan Blue Exclusion Method ◽  
Ic50 Value ◽  
Ic50 Values

Osteosarcoma is the most commonly diagnosed malignant bone tumor in humans, with a higher incidence in children and young people. It is highly aggressive and has a high metastatic potential. Its treatment is based on both chemotherapy and surgical intervention. However, currently used chemotherapeutic agents, such as doxorubicin, have several adverse effects on the patient. Therefore, there is a growing demand for new chemotherapeutic agents that stimulate new researches, such as those involving compounds extracted from plants, such as the gabirobeira. In this study, we aimed to evaluate the cytotoxic effects of ethanolic extract, both crude and ethyl acetate, of gabirobeira leaves on osteosarcoma cells in vitro. Cytotoxicity was evaluated using the Trypan blue exclusion method and the IC50 values were calculated using the tetrazolium reduction method. The ethanolic extract of gabirobeira leaves showed a cytotoxic effect on osteosarcoma cells in vitro. The group treated with the crude extract at 1. 0μL mL-1 concentration for 48 hours showed higher cytotoxicity and the lowest IC50 value for this extract was found in the 24 to 48 hours interval. The ethanolic extract of gabirobeira leaves is cytotoxic for osteosarcoma cells.

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.

Anti-plasmodial Effects of Zanthoxylum zanthoxyloides

Planta Medica ◽  
2019 ◽  
Vol 85 (13) ◽  
pp. 1073-1079 ◽  
Author(s):  
Christopher Dean Goodman ◽  
An Thuy Hoang ◽  
Drissa Diallo ◽  
Karl Egil Malterud ◽  
Geoffrey I. McFadden ◽  
...  
Keyword(s):  
Brine Shrimp ◽  
Methanol Extract ◽  
Stem Bark ◽  
Artemia Salina ◽  
Root Bark ◽  
Ic50 Values ◽  
Zanthoxylum Zanthoxyloides ◽  
Parasitic Activity ◽  
Resistant Strains

Abstract Zanthoxylum zanthoxyloides, syn. Fagara zanthoxyloides, is a tree growing in West Africa and is used in traditional medicine against a variety of diseases, including malaria. In the work reported here, root bark and stem bark extracts of this tree, as well as compounds isolated from the extracts, have been investigated for activity in vitro against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, toxicity against nauplii of the brine shrimp Artemia salina has been studied. Dichloromethane extracts of the root bark and stem bark, and a methanol extract of the stem bark, showed anti-parasitic activity towards chloroquine-sensitive as well as chloroquine-resistant P. falciparum, with IC50 values between 1 and 10 µg/mL. Among the isolated compounds, bis-dihydrochelerythrinyl ether, buesgenine, chelerythrine, γ-fagarine, skimmianine, and pellitorine were the most active, with IC50 values of less than 5 µg/mL. The dichloromethane extracts were toxic to brine shrimp nauplii, with LC50 values of less than 1 µg/mL. Methanol extracts were much less toxic (LC50 between 50 and 100 µg/mL). Among the isolated substances, bis-dihydrochelethrinyl ether was the most toxic (LC50 ca. 2 µg/mL).

Trichothecenes from an Endophytic Fungus Alternaria sp. sb23

Planta Medica ◽  
2020 ◽  
Vol 86 (13/14) ◽  
pp. 976-982
Author(s):  
Ying Gao ◽  
Jia Zhou ◽  
Hanli Ruan
Keyword(s):  
Endophytic Fungus ◽  
In Vitro Cytotoxicity ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Effects ◽  
Ic50 Values ◽  
Alternaria Sp ◽  
Optical Rotations ◽  
Ht 29 ◽  
Necrosis Factor

AbstractThree new (alterchothecenes A – C, 1 –3) and 3 known (4 –6) trichothecenes, along with 9 known compounds (7 –15), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 1–3 were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 1–6 against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 4–6 exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 1–6 as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 1–6 synergistically decreased cell viability compared with the sole treatment with those compounds.

scholarly journals Differential cytotoxicity of iron chelators on malaria-infected cells versus mammalian cells

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4871-4878 ◽  
Author(s):  
H Glickstein ◽  
W Breuer ◽  
M Loyevsky ◽  
AM Konijn ◽  
A Shanzer ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Chemotherapeutic Agents ◽  
Iron Chelators ◽  
Intracellular Iron ◽  
In Vitro Proliferation ◽  
Ic50 Values ◽  
Infected Cells ◽  
Cell Cytosol ◽  
Improved Design

Iron chelators of the hydroxamate class arrest in vitro proliferation of malaria parasites end of mammalian cells. The factors determining the biological activity of the chelators have classically been attributed to the chelators' capacity for binding iron and to their ability to traverse membranes as free chelators and as chelator-iron complexes. We show in this work that the nature of the chelatable pool of cell iron also contributes to the susceptibility of cells to iron chelators. A class of N-terminal (Nt derivatives of desferrioxamine (DFO), (Nt-DFO), is shown here to differentially affect growth and replication of intraerythrocytic parasites (Plasmodium falciparum). Methyl-anthranilic DFO (MADFO), the relatively less hydrophilic member of the Nt-DFOs series, reduced parasite proliferation (48 hour test) with an IC50 of 4 +/- 1 micromol/L and mammalian cell (K562 and HepG2) proliferation with an IC50 > 100 micromol/L. On the other hand, the more hydrophilic Nt-free DFO, displayed IC50 values of 21 +/- 5 micromol/L for parasites and 7 +/- 1 micromol/L for mammalian cells. The selective antiparasitic activity of MA-DFO, as reflected in the speed of action and IC50 values on cell proliferation, is attributed primarily to membrane permeation and iron (III) binding properties of the drug. In contrast, the relatively low antiproliferative activity of the more permeant MA-DFO on mammalian cells, resulted from MA-DFO's reduced capacity for scavenging intracellular iron. This is apparent from MA-DFO reduced effects on: (1) the chelatable iron (II) pool that is associated with the cell cytosol; (2) the cell chelator-extractable iron, and (3) cell ferritin levels. The potent antimalarial efficacy and biological selectivity of MA-DFO relative to the parent DFO, is of importance for improved design of chemotherapeutic agents.

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