Antimalarial activity of Curcuma caesia against 3D7 and K1 strains of Plasmodium falciparum

Abstract Background: Malaria is one of the severe tropical disease and majority of deaths occurred due to Plasmodium falciparum. Lack of a vaccine and the widespread resistance to antimalarial drugs have resulted in emphasis on novel antimalarial drugs development. The purpose of the study was to evaluate in vitro and in-silico antiplasmodial potential of Curcuma caesia extracts against P. falciparum.Methods: Ethyl acetate and methanol extracts of C. caesia were prepared and analysed for their antiplasmodial activity against Chloroquine sensitive (3D7) and resistant (K1) strains of P. falciparum using fluorescence-based SYBR Green assay. The cytotoxicity tests were carried out using the vero cell lines by MTT assay. The phosphoethanolamine methyltransferase enzyme ((PfPMT) essential for growth of P. falciparum was used as protein target for in-silico study. Result: C. caesia ethyl acetate extracts showed the potent antiplasmodial activity with IC50 values of 3.37 µg/ml and 1.53 µg/ml against 3D7 and K1 strain respectively. The IC50 values of methanol extract were reported, 8.57 µg/ml against 3D7 and 18.29 µg/ml against K1 strains The cytotoxicity assay revealed that the extracts were not toxic against vero cell lines as the CC50 values were less than IC50. Docking results show that β-selinenol an oxygenized sesquiterpene present in C. caesia had the free binding energy of -6.76 Kcal/mol.Conclusion: The compounds β-selinenol, α-eudesmol, α –acorenol, boldione and xanthinin present in the C. caesia extract possess antimalarial potential being inhibitor of PfPMT. The present findings, however preliminary in nature. Further studies are needed to identify the active compounds and in vivo mechanism to prove the antimalarial efficacy of C. caesia in the development of antimalarial drugs.

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Antimalarial Activity of Curcuma Caesia Against 3D7 and K1 Strains of Plasmodium Falciparum

10.21203/rs.3.rs-32452/v1 ◽

2020 ◽

Author(s):

Monika Chaturvedi ◽

Reena Rani ◽

Dushyant Sharma ◽

Jaya Parkash Yadav

Keyword(s):

Plasmodium Falciparum ◽

Ethyl Acetate ◽

In Silico ◽

Antimalarial Activity ◽

Antimalarial Drugs ◽

Mechanism Study ◽

Effective Development ◽

Ethyl Acetate Extracts

Abstract Background: Malaria is a severe and sometimes mortal tropical disease that spreads through parasites. The purpose of the study was to evaluate in vitro and in-silicoantiplasmodial potential of Curcuma caesia extracts against Plasmodium falciparum.Methods: Lack of a vaccine and the widespread resistance to antimalarial drugs have resulted in emphasis on novel antimalarial drugs development. Ethyl acetate and methanol extracts of Curcuma caesia were prepared and analysed for their antiplasmodial activity against Chloroquine sensitive (3D7) and resistant (K1) strains of P. falciparumusingfluorescence-based SYBR Green assay. The cytotoxicity tests were carried out using the verocell lines by MTT assay.The phosphoethanolamine methyltransferase enzyme ((PfPMT) essential for growth of Plasmodium falciparum was used as protein target for in-silicostudy.Result: Curcuma caesia ethyl acetate extracts showedpotentantiplasmodial activitywith IC50 values of 3.37 µg/ml and 1.53 µg/ml against 3D7 and K1 strain respectively.Docking results show that β-selinenol an oxygenized sesquiterpene had the free binding energy of -6.76 Kcal/mol.Conclusion: Sesquiterpene present in the Curcuma caesia extract was responsible for antimalarial potential analyzed by molecular modeling. The present findings, however preliminary in nature. Further studies are required to proven the antimalarial efficacy C. caesia by isolating the active compounds and in vivo mechanism study that may contribute to more effective development of antimalarial drugs in the future.

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In Vitro Assessment of Antiplasmodial Activity and Cytotoxicity of Polyalthia longifolia Leaf Extracts on Plasmodium falciparum Strain NF54

Malaria Research and Treatment ◽

10.1155/2019/6976298 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Bethel Kwansa-Bentum ◽

Kojo Agyeman ◽

Jeffrey Larbi-Akor ◽

Claudia Anyigba ◽

Regina Appiah-Opong

Keyword(s):

Plasmodium Falciparum ◽

Ethyl Acetate ◽

Red Blood Cells ◽

Blood Cells ◽

Radical Scavenging ◽

Antimalarial Drugs ◽

Antiplasmodial Activity ◽

Leaf Extracts ◽

Polyalthia Longifolia

Background. Malaria is one of the most important life-threatening infectious diseases in the tropics. In spite of the effectiveness of artemisinin-based combination therapy, reports on reduced sensitivity of the parasite to artemisinin in Cambodia and Thailand warrants screening for new potential antimalarial drugs for future use. Ghanaian herbalists claim that Polyalthia longifolia has antimalarial activity. Therefore, antiplasmodial activity, cytotoxic effects, and antioxidant and phytochemical properties of P. longifolia leaf extract were investigated in this study. Methodology/Principal Findings. Aqueous, 70% hydroethanolic and ethyl acetate leaf extracts were prepared using standard procedures. Antiplasmodial activity was assessed in vitro by using chloroquine-sensitive malaria parasite strain NF54. The SYBR® Green and tetrazolium-based calorimetric assays were used to measure parasite growth inhibition and cytotoxicity, respectively, after extract treatment. Total antioxidant activity was evaluated using a free radical scavenging assay. Results obtained showed that extracts protected red blood cells against Plasmodium falciparum mediated damage. Fifty percent inhibitory concentration (IC50) values were 24.0±1.08 μg/ml, 22.5±0.12 μg/ml, and 9.5±0.69 μg/ml for aqueous, hydroethanolic, and ethyl acetate extracts, respectively. Flavonoids, tannins, and saponins were present in the hydroethanolic extract, whereas only the latter was observed in the aqueous extract. Aqueous and hydroethanolic extracts showed stronger antioxidant activities compared to the ethyl acetate extract. Conclusions/Significance. The extracts of P. longifolia have antiplasmodial properties and low toxicities to human red blood cells. The extracts could be developed as useful alternatives to antimalarial drugs. These results support claims of the herbalists that decoctions of P. longifolia are useful antimalarial agents.

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Synthesis, Plasmodium falciparum Inhibitory Activity, Cytotoxicity and Solubility of N2 ,N4 -Disubstituted Quinazoline-2,4-diamines.

Medicinal Chemistry ◽

10.2174/1573406415666181219100307 ◽

2019 ◽

Vol 15 (6) ◽

pp. 693-704 ◽

Cited By ~ 1

Author(s):

Nattakarn Pobsuk ◽

Praphasri Suphakun ◽

Supa Hannongbua ◽

Chanin Nantasenamat ◽

Kiattawee Choowongkomon ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Physical Properties ◽

Vero Cell ◽

Cell Lines ◽

Inhibitory Activity ◽

Antimalarial Activity ◽

Control Strategies ◽

Treatment Options ◽

Mammalian Cell Lines ◽

Vero Cell Lines

Background: Despite the development of extensive control strategies and treatment options, approximately 200 million malaria cases, leading to approximately 450,000 deaths, were reported in 2015. Due to issue of disease resistance, additional drug development efforts are needed to produce new, more effective treatments. Quinazoline-2,4-diamines were identified as antiparasitic compounds over three decades ago and have remained of interest to date in industry and academia. Objective: An anti-malarial SAR evaluation of previously unreported N2 ,N4 -disubstituted quinazoline- 2,4-diamines have been undertaken in this study. We have synthesized and evaluated new derivatives against P. falciparum in our attempt to better characterize their biological activity and overall physical properties. Methods: The synthesis of N2 ,N4 -disubstituted quinazoline-2,4-diamines inhibitors is reported along with activities in a radioactive labeled hypoxanthine incorporation assay against the f Plasmodium falciparum (Pf.) K1 strain. In addition, cytotoxicity was determined in the A549 and Vero cell lines using an MTT based. The aqueous solubility of key compounds was assessed at pH 7.4 using a shake flask-based approach. Results: We identified compounds 1 and 6p as sub µM inhibitors of P. falciparum, having equivalent anti-malarial activity to Chloroquine. Compounds 1 and 6m are low µM inhibitors of P. falciparum with improved cytotoxicity profiles. Compound 6m displayed the best balance between P. falciparum Inhibitory activity (2 µM) and cytotoxicity, displaying >49 fold selectivity over A549 and Vero cell lines. Conclusion: Twenty one N2 ,N4 -Disubstituted Quinazoline-2,4-diamines have been prepared in our group and characterized in terms of their antimalarial activity, cytotoxicity and physical properties. Compounds with good activity and reasonable selectivity over mammalian cell lines have been identified. SAR analyses suggest further exploration is are necessary to improve the balance of P. falciparum Inhibitory activity, cytotoxicity and solubility.

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Synthesis and Antimalarial Activity of 2-Phenyl-1,10-Phenanthroline Derivative Compounds

Jurnal Natur Indonesia ◽

10.31258/jnat.15.1.57-62 ◽

2014 ◽

Vol 15 (1) ◽

pp. 57

Author(s):

Ruslin Hadanu ◽

Mustofa Mustofa ◽

Nazudin Nazudin

Keyword(s):

Plasmodium Falciparum ◽

Dimethyl Sulphate ◽

Antimalarial Activity ◽

Antimalarial Drugs ◽

Starting Material ◽

Antiplasmodial Activity ◽

Second Step ◽

The Third ◽

Fcr3 Strain

To develop new potential antimalarial drugs of 2-phenyl-1,10-phenanthroline 5 derivatives from 8-aminoquinoline as startingmaterial were synthesized in good yields. The synthesis of 2-phenyl-1,10-phenanthroline 5 derivatives compoundswith 8-aminoquinoline 4 as starting material through three steps has been carried out. The first step of reactions is aldolcondensation of benzaldehyde 1 with acetaldehyde 2. The result of reactions is cinnamaldehyde 3 (92.14%) in the form ofyellow solid. The second step of reactions was synthesized of 2-phenyl-1,10-phenanthroline 5 (brown solid, 54.63%)through cyclization of 8-aminoquinoline 4 with cinnamaldehyde 3 compound. The third step of reactions is methylation andethylation of 2-phenyl-1,10-phenanthroline using dimethyl sulphate (DMS) and diethyl sulphate (DES) reagents that it wasrefluxed for 17 and 19 h, respectively. The results of reactions are (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6and (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 in yield from 90.62% and 89.70%, respectively. The results oftesting in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum FCR3 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 compound has higherantimalarial activity (IC 50 :0.13 ± 0.02 μM) than antimalarial activity of (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate6 compound (IC 50 :0.25 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :2.45 ± 0.09 μM). While, the resultsof testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum D10 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 compound has higherantimalarial activity (IC 50 :0.10± 0.04 μM) than antimalarial activity of (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate7 (IC 50 :0.18 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :0.55 ± 0.07 μM).

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Inside Cover: Docking Studies of Structurally Diverse Antimalarial Drugs Targeting PfATP6: No Correlation between in silico Binding Affinity and in vitro Antimalarial Activity. (ChemMedChem 9/2009)

ChemMedChem ◽

10.1002/cmdc.200990042 ◽

2009 ◽

Vol 4 (9) ◽

pp. 1386-1386

Author(s):

Fatima Bousejra-El Garah ◽

Jean-Luc Stigliani ◽

Frédéric Coslédan ◽

Bernard Meunier ◽

Anne Robert

Keyword(s):

Binding Affinity ◽

In Silico ◽

Antimalarial Activity ◽

Docking Studies ◽

Antimalarial Drugs

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Effect of Different Hydatid Cyst Molecules on Hela and Vero Cell Lines Growth In vitro

Journal of Immunodeficiency & Disorders ◽

10.4172/2324-853x.1000105 ◽

2013 ◽

Vol 02 (01) ◽

Cited By ~ 4

Author(s):

Nasir Aref ◽

Hedayatollah Shirzad ◽

Morteza Yousefi ◽

Hossein Yousofi.Darani

Keyword(s):

Hydatid Cyst ◽

Vero Cell ◽

Cell Lines ◽

Vero Cell Lines

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Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02041-19 ◽

2020 ◽

Vol 64 (9) ◽

Author(s):

Letícia Tiburcio Ferreira ◽

Juliana Rodrigues ◽

Gustavo Capatti Cassiano ◽

Tatyana Almeida Tavella ◽

Kaira Cristina Peralis Tomaz ◽

...

Keyword(s):

Plasmodium Falciparum ◽

In Silico ◽

Antimalarial Activity ◽

Drug Repositioning ◽

Dna Gyrase ◽

Plasmodium Yoelii ◽

Computer Assisted ◽

Content Type

ABSTRACT Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks, and time-to-market. Herein, we have used this strategy to identify novel antimalarial hits. We used a comparative in silico chemogenomics approach to select Plasmodium falciparum and Plasmodium vivax proteins as potential drug targets and analyzed them using a computer-assisted drug repositioning pipeline to identify approved drugs with potential antimalarial activity. Among the seven drugs identified as promising antimalarial candidates, the anthracycline epirubicin was selected for further experimental validation. Epirubicin was shown to be potent in vitro against sensitive and multidrug-resistant P. falciparum strains and P. vivax field isolates in the nanomolar range, as well as being effective against an in vivo murine model of Plasmodium yoelii. Transmission-blocking activity was observed for epirubicin in vitro and in vivo. Finally, using yeast-based haploinsufficiency chemical genomic profiling, we aimed to get insights into the mechanism of action of epirubicin. Beyond the target predicted in silico (a DNA gyrase in the apicoplast), functional assays suggested a GlcNac-1-P-transferase (GPT) enzyme as a potential target. Docking calculations predicted the binding mode of epirubicin with DNA gyrase and GPT proteins. Epirubicin is originally an antitumoral agent and presents associated toxicity. However, its antiplasmodial activity against not only P. falciparum but also P. vivax in different stages of the parasite life cycle supports the use of this drug as a scaffold for hit-to-lead optimization in malaria drug discovery.

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Autophagic Cell Death Is Induced by Acetone and Ethyl Acetate Extracts fromEupatorium odoratum In Vitro: Effects on MCF-7 and Vero Cell Lines

The Scientific World JOURNAL ◽

10.1100/2012/439479 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Faizah Bt. Harun ◽

Syed Mohsin Syed Sahil Jamalullail ◽

Khoo Boon Yin ◽

Zulkhairi Othman ◽

Anita Tilwari ◽

...

Keyword(s):

Cell Death ◽

Ethyl Acetate ◽

Cytotoxic Activity ◽

Vero Cell ◽

Cell Lines ◽

Autophagic Cell Death ◽

Biologically Active ◽

Vero Cell Lines ◽

Mcf 7 ◽

Ethyl Acetate Extracts

Eupatorium odoratum (EO)contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action ofEOextracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 μg/mL. These results thus suggest that acetone and ethyl acetate extracts ofEOinduce cell death through induction of autophagy and hold potential for development as potential anticancer drugs.

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