scholarly journals Evaluation Of Potential Cytotoxic Effects Of Herbal Extracts

2015 ◽  
Vol 16 (4) ◽  
pp. 333-342 ◽  
Author(s):  
Ana Radovanovic
Keyword(s):  
Cytotoxic Activity ◽  
Cytotoxic Effect ◽  
Chemical Constituents ◽  
Solvent Polarity ◽  
New Drugs ◽  
Herbal Extract ◽  
Signalling Pathways ◽  
Herbal Extracts ◽  
Starting Point ◽  
Influence Of Solvent

Abstract Herbal medicines have played an important role in treating different diseases since ancient times. Bioactive components of medicinal plants are a good starting point for discovering new drugs such as chemotherapeutics. Currently, there are four classes of plant-derived chemotherapeutic drugs used in clinical practice. However, to discover new potential cytotoxic molecules, the research effort on herbal extracts has not diminished. The aim of this review was to evaluate the chemical constituents of plants that possess cytotoxicity, the signalling pathways responsible for this effect, and the influence of solvent polarity on potential cytotoxic effect and to present the cytotoxic activity of selected herbal extracts. The polyphenolic, anthraquinon, diterpneoid, triterpenoid, flavonoid, betulinic acid and berberine content contributes to cytotoxicity of herbal extracts. The inhibitory effect on cancer cells viability could be a consequence of the non-apoptotic processes, such as cell cycle arrestment, and the apoptotic process in tumour cells through different signalling pathways. The influence of solvent polarity on potential cytotoxic effect of herbal extracts should not be ignored. In general, the best cytotoxic activity was found in nonpolar and moderately polar herbal extracts. The herbal extract with IC50 below 30 μg/ml could be considered a very strong cytotoxic agent. Considering that many antitumor drugs have been discovered from natural products, further research on plants and plant-derived chemicals may result in the discovery of potent anticancer agents.

scholarly journals Benzimidazole Derivatives as New and Selective Inhibitors of Arginase from Leishmania mexicana with Biological Activity against Promastigotes and Amastigotes

2021 ◽  
Vol 22 (24) ◽  
pp. 13613
Author(s):  
Irene Betancourt-Conde ◽  
Claudia Avitia-Domínguez ◽  
Alicia Hernández-Campos ◽  
Rafael Castillo ◽  
Lilián Yépez-Mulia ◽  
...  
Keyword(s):  
Biological Activity ◽  
In Silico ◽  
Cytotoxic Effect ◽  
New Drugs ◽  
Dynamics Simulation ◽  
Benzimidazole Derivatives ◽  
Leishmania Mexicana ◽  
Arginase 1 ◽  
Excellent Starting Point ◽  
Starting Point

Leishmaniasis is a disease caused by parasites of the Leishmania genus that affects 98 countries worldwide, 2 million of new cases occur each year and more than 350 million people are at risk. The use of the actual treatments is limited due to toxicity concerns and the apparition of resistance strains. Therefore, there is an urgent necessity to find new drugs for the treatment of this disease. In this context, enzymes from the polyamine biosynthesis pathway, such as arginase, have been considered a good target. In the present work, a chemical library of benzimidazole derivatives was studied performing computational, enzyme kinetics, biological activity, and cytotoxic effect characterization, as well as in silico ADME-Tox predictions, to find new inhibitors for arginase from Leishmania mexicana (LmARG). The results show that the two most potent inhibitors (compounds 1 and 2) have an I50 values of 52 μM and 82 μM, respectively. Moreover, assays with human arginase 1 (HsARG) show that both compounds are selective for LmARG. According to molecular dynamics simulation studies these inhibitors interact with important residues for enzyme catalysis. Biological activity assays demonstrate that both compounds have activity against promastigote and amastigote, and low cytotoxic effect in murine macrophages. Finally, in silico prediction of their ADME-Tox properties suggest that these inhibitors support the characteristics to be considered drug candidates. Altogether, the results reported in our study suggest that the benzimidazole derivatives are an excellent starting point for design new drugs against leishmanisis.

scholarly journals Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

2020 ◽  
Author(s):  
Awet Alem Teklemichael ◽  
Shusaku Mizukami ◽  
Kazufumi Toume ◽  
Farhana Mosaddeque ◽  
Mohamed Gomaa Kamel ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Active Compound ◽  
Antimalarial Activity ◽  
New Drugs ◽  
Herbal Extract ◽  
Herbal Extracts ◽  
Vitro Assay ◽  
Malaria Model

Abstract Background: The herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, examined a variety of Japanese traditional herbal medicine (Kampo) for their potential antimalarial activities. Methods: We designed a comprehensive screening to identify novel antimalarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n=96). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and -resistant (Dd2) strains of Plasmodium falciparum . The cytotoxicity was also evaluated using primary Adult Mouse Brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo antimalarial activity. Results: Out of 120 herbal extracts, Coptis Rhizome showed the highest antimalarial activity (IC 50 1.9 µg/mL of 3D7 and 4.85 µg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis Rhizome also showed antimalarial activities with IC 50 1.1, 2.6, and 6.0 µM (against 3D7) and 3.1, 6.3, and 11.8 µM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest antimalarial activity (IC 50 1.1 µM against 3D7 and 3.1 µM against Dd2) with SI of 37.8 and 13.2, respectively. . Finally, the herbal extract of Coptis Rhizome and its major active compound coptisine chloride exhibited significant antimalarial activity in mice infected with P. yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P <.05) for Coptis Rhizome and from 81 to 89% (P <.01) for coptisine chloride. Conclusion: Coptis Rhizome and its major active compound coptisine chloride showed promising antimalarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus Kampo herbal medicine is a potential natural resource for novel antipathogenic agents.

scholarly journals Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

2020 ◽  
Author(s):  
Awet Alem Teklemichael ◽  
Shusaku Mizukami ◽  
Kazufumi Toume ◽  
Farhana Mosaddeque ◽  
Mohamed Gomaa Kamel ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Active Compound ◽  
Antimalarial Activity ◽  
New Drugs ◽  
Herbal Extract ◽  
Herbal Extracts ◽  
Related Compounds ◽  
Malaria Model

Abstract Background: The herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, examined a variety of Japanese traditional herbal medicine (Kampo) for their potential antimalarial activities.Methods: We designed a comprehensive screening to identify novel antimalarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n=96). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and -resistant (Dd2) strains of Plasmodium falciparum. The cytotoxicity was also evaluated using primary Adult Mouse Brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo antimalarial activity.Results: Out of 120 herbal extracts, Coptis Rhizome showed the highest antimalarial activity (IC50 1.9 µg/mL of 3D7 and 4.85 µg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis Rhizome also showed antimalarial activities with IC50 1.1, 2.6, and 6.0 µM (against 3D7) and 3.1, 6.3, and 11.8 µM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest antimalarial activity (IC50 1.1 µM against 3D7 and 3.1 µM against Dd2) with SI of 37.8 and 13.2, respectively. . Finally, the herbal extract of Coptis Rhizome and its major active compound coptisine chloride exhibited significant antimalarial activity in mice infected with P. yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P <.05) for Coptis Rhizome and from 81 to 89% (P <.01) for coptisine chloride.Conclusion: Coptis Rhizome and its major active compound coptisine chloride showed promising antimalarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus Kampo herbal medicine is a potential natural resource for novel antipathogenic agents.

Two isoprenylated flavonoids from Dorstenia psilurus activate AMPK, stimulate glucose uptake, inhibit glucose production and lower glycemia

2019 ◽  
Vol 476 (24) ◽  
pp. 3687-3704 ◽  
Author(s):  
Aphrodite T. Choumessi ◽  
Manuel Johanns ◽  
Claire Beaufay ◽  
Marie-France Herent ◽  
Vincent Stroobant ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Human Cancer ◽  
Glucose Production ◽  
Liver Mitochondria ◽  
New Drugs ◽  
Structural Isomer ◽  
Rat Liver Mitochondria ◽  
Ionization Mass ◽  
Ampk Activation ◽  
Starting Point

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze–thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKβ1−/− mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.

Chemometric Analysis for the Classification of some Groups of Drugs with Divergent Pharmacological Activity on the Basis of some Chromatographic and Molecular Modeling Parameters

2018 ◽  
Vol 21 (2) ◽  
pp. 125-137
Author(s):  
Jolanta Stasiak ◽  
Marcin Koba ◽  
Marcin Gackowski ◽  
Tomasz Baczek
Keyword(s):  
Correlation Analysis ◽  
Pharmacological Activity ◽  
Correlation Coefficients ◽  
Principal Component ◽  
Cardiovascular Drugs ◽  
New Drugs ◽  
Analgesic Drugs ◽  
Starting Point ◽  
Chromatographic Parameters

Aim and Objective: In this study, chemometric methods as correlation analysis, cluster analysis (CA), principal component analysis (PCA), and factor analysis (FA) have been used to reduce the number of chromatographic parameters (logk/logkw) and various (e.g., 0D, 1D, 2D, 3D) structural descriptors for three different groups of drugs, such as 12 analgesic drugs, 11 cardiovascular drugs and 36 “other” compounds and especially to choose the most important data of them. Material and Methods: All chemometric analyses have been carried out, graphically presented and also discussed for each group of drugs. At first, compounds’ structural and chromatographic parameters were correlated. The best results of correlation analysis were as follows: correlation coefficients like R = 0.93, R = 0.88, R = 0.91 for cardiac medications, analgesic drugs, and 36 “other” compounds, respectively. Next, part of molecular and HPLC experimental data from each group of drugs were submitted to FA/PCA and CA techniques. Results: Almost all results obtained by FA or PCA, and total data variance, from all analyzed parameters (experimental and calculated) were explained by first two/three factors: 84.28%, 76.38 %, 69.71% for cardiovascular drugs, for analgesic drugs and for 36 “other” compounds, respectively. Compounds clustering by CA method had similar characteristic as those obtained by FA/PCA. In our paper, statistical classification of mentioned drugs performed has been widely characterized and discussed in case of their molecular structure and pharmacological activity. Conclusion: Proposed QSAR strategy of reduced number of parameters could be useful starting point for further statistical analysis as well as support for designing new drugs and predicting their possible activity.

Synthesis and Anticancer Activity of New Hydrazide-hydrazones and Their Pd(II) Complexes

2019 ◽  
Vol 16 (5) ◽  
pp. 522-532 ◽  
Author(s):  
Bedia Kocyigit-Kaymakcioglu ◽  
Senem Sinem Yazici ◽  
Fatih Tok ◽  
Miriş Dikmen ◽  
Selin Engür ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
A549 Cells ◽  
Cancer Cell Line ◽  
Fibroblast Cell ◽  
Reference Drug ◽  
A549 Cancer Cell Line

Background: Hydrazones, one of the important classes of organic molecules, are pharmaceutical agents comprising –CO-NH-N=CH- group in the structure therefore and exhibiting significant biological activity. Methods: 5-Chloro-N’-[(substituted)methylidene] pyrazine-2-carbohydrazide (3a-g) and their Pd(II) complexes (4a-h) were synthesized and investigated in vitro anticancer activity on A549, Caco2 cancer and normal 3T3 fibroblast cell lines, using the MTT assay. Results: Anticancer activity screening results revealed that some compounds showed remarkable cytotoxic effect. Among them, 5-chloro-N'-[(4-hydroxyphenyl)methylidene] pyrazine-2-carbohydrazide (3c) displayed higher cytotoxic activity against A549 cancer cell line than the reference drug cisplatin. Conclusion: Compound 3c showed high cytotoxic activity against A549 cancer cell line but it showed low cytotoxic effect against normal 3T3 fibroblast cell line. Antiproliferative and antimetastatic effects of 3c were determined by the real-time monitoring of cell proliferative system (RTCA DP). The cell proliferation, metastatic and invasive activities of A549 cells were decreased due to increased concentration of 3c.

Design of Inhibitors for Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Enzyme of Leishmania mexicana

2020 ◽  
Vol 16 (6) ◽  
pp. 784-795
Author(s):  
Krisnna M.A. Alves ◽  
Fábio José Bonfim Cardoso ◽  
Kathia M. Honorio ◽  
Fábio A. de Molfetta
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Site ◽  
Point Of View ◽  
New Drugs ◽  
Leishmania Mexicana ◽  
Receptor Complexes ◽  
Starting Point ◽  
Dynamics Simulations ◽  
Selection Of

Background:: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3- phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease. Objective:: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana). Methods: A search for novel antileishmanial molecules was carried out based on similarities from the pharmacophoric point of view related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations. Results:: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity. Conclusion:: he use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.

Phytochemical screening, cytotoxicity and anti-inflammatory activities of the leaf extracts from Lawsonia inermis of Indian origin to explore its potential for medicinal uses

2020 ◽  
Vol 16 ◽  
Author(s):  
Anju Manuja ◽  
Nitu Rathore ◽  
Shalki Chaudhary ◽  
Balvinder Kumar
Keyword(s):  
Nitric Oxide ◽  
Cytotoxic Activity ◽  
Cytotoxic Effect ◽  
Vero Cells ◽  
Nitric Oxide Production ◽  
Lawsonia Inermis ◽  
Leaf Extracts ◽  
Oxide Production ◽  
Indian Origin ◽  
Anti Inflammatory

Background: Lawsonia inermis Linn popularly known as the Henna has played an important role in ayurvedic or natural herbal medicines. The presence of phyto-constituents in henna, that may affect the animal or human health adversely, need to be elucidated for L. inermis Linn species grown in India. Introduction: Introduction: The aim of this research was to perform phytochemical, cytotoxicity and anti-inflammatory studies to understand the potential of leaves of Lawsonia inermis of Indian origin to provide a way forward for therapeutic use in medicine. Methods: We assessed the phytochemical profile for presence of phyto-constituents (alkaloids, carbohydrates, glycosides, steroids, flavonoids, saponins, tannins, proteins/amino acids and gums/mucilage) from various extracts of the plant leaves’. The extracts were further purified by column chromatography for the isolation of plant constituents and monitored by TLC, analyzed by Fourier transform infrared FT-IR spectroscopy, H1NMR, and GC-MS analysis. Fractions were assessed for cytotoxicity and anti-inflammatory properties at various concentrations. We assessed the anti-inflammatory activity by nitric oxide production in various leaf extracts determined by Griess assay. Results: All the spectral results suggest that the compounds from the extract contain aromatic nucleus and OH group along with methoxy group, allyl as well as vinyl group. Fractions of chloroform/methanolic (7:3) leaf extract of Lawsonia inermis confirmed the presence of the two constituents i.e. fraxetin and 1(3H)-isobenzofuranone. We observed significant difference in cytotoxicity at higher concentrations in methanol and chloroform:methanol (8:2) leaf extracts (p>0.05), we could not find any significant differences amongst other leaf extracts at different concentrations. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells. The nitric oxide levels decreased from 1000 µg/ml concentration to lower concentrations with varying degree. Overall the highest nitric oxide production by CHCl3 (70%)/ MeOH (30%) was observed amongst various fractions at different concentrations. Conclusion: The phytochemical, cytotoxicity and anti-inflammatory studies indicating the potential of leaves of the plant to provide a way further for their use in medicine. Fraxetin 1(3H)-isobenzofuranone structures were confirmed in fractions of CHCl3 (70%)/ MeOH (30%) extract as observed as a potent constituents. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells.The cytotoxicity studies indicates the presence of cytotoxic compounds in some of these extracts, warranting research for fabrication of suitable formulations comprising these constituents to reduce its dose/toxicity for the use of beneficial effects of the plant components.

Influence of solvent polarity on the dual fluorescence of p-N,N-dimethylaminobenzonitrile: An AM1 theoretical study

1990 ◽  
Vol 55 (8) ◽  
pp. 1891-1895 ◽  
Author(s):  
Peter Ertl
Keyword(s):  
Excited State ◽  
Theoretical Study ◽  
Solvent Polarity ◽  
Semiempirical Method ◽  
Dual Fluorescence ◽  
Long Wavelength ◽  
Polar Media ◽  
Wavelength Emission ◽  
Ground State Geometry ◽  
Influence Of Solvent

Twisting of the NMe2 group in p-N,N-dimethylaminobenzonitrile (DMABN) was investigated using AM1 semiempirical method with configuration interaction. Effect of polar media was considered by placing + and - charge centers ("sparkles") at appropriate places opposite the molecule. Optimized ground state geometry of DMABN is slightly twisted with the lowest vertical excited state of 1B character. As the polarity of media increases and/or the - NMe2 group twists, the symmetric 1A excited state having considerable charge separation becomes energetically favorable. Anomalous long-wavelength emission of DMABN comes from this state.

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