scholarly journals In Vitro Antimalarial Activity and Cytotoxity of 20 Ethanolic Crude Extracts from Thai Herbs Against Plasmodium Falciparum TM267

2017 ◽  
Vol 35 (2) ◽  
pp. 109
Author(s):  
Natharinee Horata ◽  
Sarawut Suttirat ◽  
Taweebhorn Panpanich ◽  
Anuthida Siriphor ◽  
Budsaraporn Navaprayoonvach ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Antimalarial Activity ◽  
Vero Cells ◽  
Ocimum Sanctum ◽  
Root Extract ◽  
Active Compounds ◽  
Crude Extracts ◽  
Plumbago Indica

Objective: To determine the antimalarial activity of ethanol crude extracts from 20 Thai herbs against Plasmodiumfalciparum (P. falciparum) chloroquine-resistant strain TM267. Molecular docking of the active compounds from the selected Thaiherbs were analyzed with Plasmodium falciparum dihydrofolate reductase (PfDHFR).Material and Method: An in vitro study of antimalarial activity against P. falciparum TM267 was done using a parasitelactate dehydrogenese assay, and the cytotoxic effects of extracts were tested against Vero cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The 50% inhibitory concentration (IC50) and 50%cytotoxicity concentration were calculated from the dose-response curves. Molecular docking and post-dockingwere analyzed with the x-ray crystal structure of PfDHFR-thymidylate synthase complexed with pyrimethamine,nicotinamide adenine dinucleotide phosphate and deoxyuridylate.Results: Of these, the Plumbago indica L. root extract showed high antimalarial activity, with an IC50 value of 3.7μg/ml and less cytotoxicity when tested against Vero cells, followed by the Citrus hystrix DC. fruit extract, Vitex trifoliaLinn. root extract, Ocimum sanctum L. leave extract, of Allium sativum L. bulb extract and Salacia chinensis L. stem extract,respectively. All 7 active compounds reported from these herbal extracts had high docking scores against PfDHFR.The Citrusoside C from Citrus hystrix DC. had the highest docking score.Conclusion: It could be purposed that there were active compounds in Plumbago indica L., Vitex trifolia Linn. and Citrus hystrix DC. which are potential inhibitors against malaria that could bind to the active site of PfDHFR. However, the active Citrusosides from Citrus hystrix DC. should be further investigated for their effectiveness against malaria. 

scholarly journals Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

2015 ◽  
Vol 10 (4) ◽  
pp. 917 ◽  
Author(s):  
Mukesh Kumar Kumawat ◽  
Dipak Chetia
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Resistant Strain ◽  
Antimalarial Activity ◽  
Binding Pocket ◽  
Docking Studies ◽  
Spectroscopic Techniques ◽  
Molecular Docking Studies ◽  
Activity Screening

<p class="Abstract">Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of <em>Plasmodium falciparum</em> (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.</p><p> </p>

scholarly journals A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4485
Author(s):  
Veronika R. Karpina ◽  
Svitlana S. Kovalenko ◽  
Sergiy M. Kovalenko ◽  
Oleksandr G. Drushlyak ◽  
Natalya D. Bunyatyan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Inhibitory Concentration ◽  
Antimalarial Activity ◽  
Virtual Library ◽  
Antimalarial Agents ◽  
Starting Point ◽  
In Silico Studies

For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC50 = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs.

scholarly journals Theoretical Investigation of some Antimalarial Sulfonamides as COVID-19 Drug Utilizing Computational Calculations and Molecular Docking Study

2021 ◽  
Vol 12 (1) ◽  
pp. 1208-1229
Keyword(s):  
Molecular Docking ◽  
Energy Gap ◽  
Antimalarial Activity ◽  
Theoretical Calculations ◽  
Docking Study ◽  
Mean Value ◽  
Molecular Docking Study ◽  
Active Compounds ◽  
Computational Calculations

Reactivity investigation of N-(phenylsulfonyl)acetamide derivatives with nitrogen nucleophiles to give the corresponding aminothiazole, aminooxazole, 2H-benzo[b][1,4]oxazin-3-yl, 2H-benzo[b][1,4]thiazin-3-yl, quinoxalin-2-yl, pyridin-4-ylamino, benzo[d]thiazol-2-ylthio and 1H-benzo[d]imidazol-2-ylthio derivatives; respectively. The sulphonamides were examined in vitro antimalarial activity and characterized their ADMET properties, with IC50 values of <30µ M. The synthesized sulfonamide had c-LogP values between 2 and (mean value 2.23) and MW(molecular weight) less than 400, and the common and didn’t exhibition cytotoxicity at the concentration confirmed. Sulphonamide 6a was equipped the excellent antimalarial activity through IC50=1.2µM with had the best selectivity index (9.0) due to the occurrence of quinoxaline moiety attached to the sulfonamide ring system. Additionally, the theoretical calculations of most active compounds 4a, 5c, and 6a exhibited that value of ∆ E so small which growth tendency of electron transfer from HOMO-LUMO energy gap due to existence of benzo[b][1,4]oxazin-3-yl,benzo[b][1,4]thiazin-3-yl and quinoxalin-2-yl rings attached to sulfonamide ring. Additionally, The molecular docking study of these synthesized compounds revealed small energy affinity against Plasmepsin-1 (PDBID:1j3i) and Plasmepsin-2 (PDBID:1n81) and shorter bond length. Also, the most active compounds 4a, 5c, and 6a were docked on main protease (SARS-CoV-2) (PDBID: 6lu7) and Spike Glycoprotein (SARS-CoV-2) (PDBID:6vxx) to calculate the binding energy of these fused heterocycles sulfonamides.

scholarly journals Chemical and Bioactivity Evaluation of the Bark of Neonauclea purpurea

2012 ◽  
Vol 7 (2) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Netiya Karaket ◽  
Kanyaratt Supaibulwatana ◽  
Supatsara Ounsuk ◽  
Valérie Bultel-Poncé ◽  
Van Cuong Pham ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Traditional Medicine ◽  
Resistant Strain ◽  
Antimalarial Activity ◽  
Indole Alkaloids ◽  
Vero Cells ◽  
Stem Bark ◽  
Meoh Extract ◽  
Bioassay Guided Fractionation

Bioassay-guided fractionation of the MeOH extract from the stem bark of Neonauclea purpurea used in traditional medicine, resulted in the isolation of 2 indole alkaloids, cadambine (1) and α-dihydrocadambine (2), as well as a quinolic compound, 2,6-dimethoxy-1,4-benzoquinone (3). Antimalarial activity evaluation showed that compounds 2 and 3 exhibited mild in vitro antimalarial activity against Plasmodium falciparum, the chloroquine-resistant strain K1 with IC50 values of 6.6 and 11.3 μM, respectively. Compounds 1 and 2 showed no cytotoxicity to monkey (Vero) cells, but compound 3 showed weak cytotoxicity with an IC50 value of 1.19 μM.

scholarly journals In vitro antimalarial activity of six Aspidosperma species from the state of Minas Gerais (Brazil)

2012 ◽  
Vol 84 (4) ◽  
pp. 899-910 ◽  
Author(s):  
Maria Fâni Dolabela ◽  
Salma G. Oliveira ◽  
José M. Peres ◽  
José M.S. Nascimento ◽  
Marinete M. Póvoa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Minas Gerais ◽  
The State ◽  
Active Compounds ◽  
Human Malaria ◽  
Plant Parts ◽  
Ic50 Values

Ethnomedicinal informations point to some Aspidosperma species (Apocynaceae) as antimalarial plants in Brazil and have motivated the evaluation of six species which were collected in the state of Minas Gerais: A. cylindrocarpon Müll. Arg., A. parvifolium A. DC., A. olivaceum Müll. Arg., A. ramiflorum Müll. Arg., A. spruceanum Benth. ex Müll. Arg. and A. tomentosum Mart.. A total of 23 extracts of different plant parts in different solvents were assayed in vitro against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. All the extracts were shown to be active with IC50 values in the range of 5.0 ± 0 2.8 µg/mL to 65.0 ± 4.2 µg/mL. TLC profile of the extracts revealed the presence of alkaloids in the six species assayed. These results seem to confirm the popular use of Aspidosperma species to treat human malaria in Brazil and seem point to alkaloids as the putative active compounds of the assayed species.

scholarly journals Phytochemical, Biological and Computational Investigations of Erythrina fusca Lour. to Assess Antimalarial Property against Plasmodium falciparum

2020 ◽  
Author(s):  
Saiful Arefeen Sazed ◽  
Ohedul Islam ◽  
Sarah L. Bliese ◽  
Muhammad Riadul Haque Hossainey ◽  
Mahfuza Afroz Soma ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Antimalarial Drug ◽  
Antimalarial Activity ◽  
Drug Candidate ◽  
Separation And Purification ◽  
Membrane Stabilization ◽  
Phytochemical Investigation ◽  
Biological Tests

For centuries medicinal plants have been traditionally used for prophylaxis and ailment of diseases. Nowadays it&rsquo;s easy to isolate, purify, and characterize bioactive compounds with high efficacy. To investigate the medicinal especially antimalarial property of traditionally used plants, a number of Erythrina spp have been reviewed systematically where Erythrina fusca has been selected for further analysis. Phytochemical investigation included chromatographic separation and purification of compounds followed by characterization using NMR. In-vitro antimalarial drug sensitivity ELISA was carried out against chloroquine (CQ) sensitive 3D7 and resistant Dd2 strains. Additional biological tests such as central and peripheral analgesic, antioxidant, anti-diarrheal, hypoglycemic, thrombolytic, and membrane stabilization activities were also investigated. Molecular docking was performed using the isolated compounds against clinically important 14 Plasmodium falciparum proteins. For the first time, Phaseolin, Phytol, &beta;-amyrin, Lupeol, and Stigmasterol are reported here and extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC50 4.94-22 &micro;g/mL). Potent central analgesic, antioxidant and anti-diarrheal activities (p&amp;lt;0.05) and mild thrombolytic and membrane stabilization properties were also observed. Molecular docking of Phaseolin bolsters its potential as a new antimalarial drug candidate. This study projects significant medicinal values and necessitates further investigations to reveal its potential as a novel source of therapeutics.

scholarly journals Antimalarial properties and molecular docking analysis of compounds from Dioscorea bulbifera L. as new antimalarial agent candidates

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Prapaporn Chaniad ◽  
Mathirut Mungthin ◽  
Apirak Payaka ◽  
Parnpen Viriyavejakul ◽  
Chuchard Punsawad
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Active Site ◽  
Antimalarial Activity ◽  
Vero Cells ◽  
Strong Hydrogen Bond ◽  
Uptake Inhibition ◽  
Pure Compounds ◽  
Dioscorea Bulbifera

Abstract Background At present, the emergence and spread of antimalarial drug resistance has become a significant problem worldwide. There has been a challenge in searching for natural products for the development of novel antimalarial drugs. Therefore, this study aims to evaluate compounds from Dioscorea bulbifera responsible for antimalarial properties and investigate potential interactions of the compounds with Plasmodium falciparum lactate dehydrogenase (PfLDH), an essential glycolytic enzyme in the parasite’s life cycle. Methods An in vitro study of antimalarial activity against chloroquine (CQ)-resistant Plasmodium falciparum (K1 strain) and CQ-sensitive P. falciparum (3D7 strain) was performed using the 3H-hypoxanthine uptake inhibition method. The cytotoxic effects of the pure compounds were tested against Vero cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The interactions of the compounds with the PfLDH active site were additionally investigated using a molecular docking method. Results Quercetin (6) exhibited the highest antimalarial activity against the P. falciparum K1 and 3D7 strains, with IC50 values of 28.47 and 50.99 μM, respectively. 2,4,3′,5′-Tetrahydroxybibenzyl (9), 3,5-dimethoxyquercetin (4) and quercetin-3-O-β-D-galactopyranoside (14) also possessed antimalarial effects against these two strains of P. falciparum. Most pure compounds were nontoxic against Vero cells at a concentration of 80 μg/ml, except for compound 9, which had a cytotoxic effect with a CC50 value of 16.71 μM. The molecular docking results indicated that 9 exhibited the best binding affinity to the PfLDH enzyme in terms of low binding energy (− 8.91 kcal/mol) and formed strong hydrogen bond interactions with GLY29, GLY32, THR97, GLY99, PHE100, THR101 and ASN140, amino acids as active sites. In addition, 6 also possessed remarkable binding affinity (− 8.53 kcal/mol) to PfLDH by interacting with GLY29, ILE31, ASP53, ILE54, THR97 and THR101. Conclusion Quercetin is a major active compound responsible for the antimalarial activity of D. bulbifera and is an inhibitor of PfLDH. These findings provide more evidence to support the traditional use of D. bulbifera for malaria treatment. Structural models of its interactions at the PfLDH active site are plausibly useful for the future design of antimalarial agents.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

1996 ◽  
Vol 40 (9) ◽  
pp. 2094-2098 ◽  
Author(s):  
B Pradines ◽  
F Ramiandrasoa ◽  
L K Basco ◽  
L Bricard ◽  
G Kunesch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mechanism Of Action ◽  
Ribonucleotide Reductase ◽  
Antimalarial Activity ◽  
Iron Chelators ◽  
Resistant Clone ◽  
Iron Deprivation ◽  
Level Of Activity ◽  
Susceptible Clone

The activities of novel iron chelators, alone and in combination with chloroquine, quinine, or artemether, were evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum with a semimicroassay system. N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7) demonstrated the highest level of activity: 170 nM against a chloroquine-susceptible clone and 1 microM against a chloroquine-resistant clone (50% inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on the activities of chloroquine, quinine, and artemether against either clone, and compound 8 did not enhance the schizontocidal action of either chloroquine or quinine against the chloroquine-resistant clone. The incubation of compound 7 with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound 7, while no effect was observed with incubation of compound 7 with CuSO4 and ZnSO4. These results suggest that iron deprivation may be the main mechanism of action of compound 7 against the malarial parasites. Chelator compounds 7 and 8 primarily affected trophozoite stages, probably by influencing the activity of ribonucleotide reductase, and thus inhibiting DNA synthesis.

scholarly journals In vitro cytotoxicity of Aspilia pluriseta Schweinf. extract fractions

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sospeter N. Njeru ◽  
Jackson M. Muema
Keyword(s):  
Biological Activities ◽  
Vero Cells ◽  
In Vitro Cytotoxicity ◽  
Root Extract ◽  
Lack Of Information ◽  
Information Gap ◽  
Diphenyltetrazolium Bromide ◽  
Potential Use

Abstract Objectives We and others have shown that Aspilia pluriseta is associated with various biological activities. However, there is a lack of information on its cytotoxicity. This has created an information gap about the safety of A. pluriseta extracts. As an extension to our recent publication on the antimicrobial activity and the phytochemical characterization of A. pluriseta root extracts, here we report on cytotoxicity of tested solvent fractions. We evaluated the potential cytotoxicity of these root extract fractions on Vero cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results We show that all solvent extract fractions (except methanolic solvent fractions) had cytotoxic concentration values that killed 50% of the Vero cells (CC50) greater than 20 µg/mL and selectivity index (SI) greater than 1.0. Taken together, we demonstrate that, A. pluriseta extract fractions’ earlier reported bioactivities are within the acceptable cytotoxicity and selective index limits. This finding scientifically validates the potential use of A. pluriseta in the discovery of safe therapeutics agents.

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