HPLC Fingerprint Analysis with in - vitro Antimalarial Activity and Bioassay Guided Fractionation of Two Organic Extract from Ageratum conyzoides Leaves

Bioassay-guided fractionation of an EtOAc extract of the broth of the endophytic fungus Nemania sp. UM10M (Xylariaceae) isolated from a diseased Torreya taxifolia leaf afforded three known cytochalasins, 19,20-epoxycytochalasins C (1) and D (2), and 18-deoxy-19,20-epoxy-cytochalasin C (3). All three compounds showed potent in vitro antiplasmodial activity and phytotoxicity with no cytotoxicity to Vero cells. These compounds exhibited moderate to weak cytotoxicity to some of the cell lines of a panel of solid tumor (SK-MEL, KB, BT-549, and SK-OV-3) and kidney epithelial cells (LLC-PK11). Evaluation of in vivo antimalarial activity of 19,20-epoxycytochalasin C (1) in a mouse model at 100 mg/kg dose showed that this compound had weak suppressive antiplasmodial activity and was toxic to animals.

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Chemical and Bioactivity Evaluation of the Bark of Neonauclea purpurea

Natural Product Communications ◽

10.1177/1934578x1200700208 ◽

2012 ◽

Vol 7 (2) ◽

pp. 1934578X1200700 ◽

Cited By ~ 1

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.

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Potent In Vitro Antimalarial Activity of Metacycloprodigiosin Isolated from Streptomycesspectabilis BCC 4785

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.4.1112-1113.2002 ◽

2002 ◽

Vol 46 (4) ◽

pp. 1112-1113 ◽

Cited By ~ 61

Author(s):

Masahiko Isaka ◽

Amonlaya Jaturapat ◽

Jarin Kramyu ◽

Morakot Tanticharoen ◽

Yodhathai Thebtaranonth

Keyword(s):

Inhibitory Concentration ◽

Antimalarial Activity ◽

Fermentation Broth ◽

Vitro Activity ◽

In Vitro Activity ◽

Antimalarial Agents ◽

Bioassay Guided Fractionation

ABSTRACT Bioassay-guided fractionation of the extract from the fermentation broth of Streptomyces spectabilis BCC 4785 led to the isolation of three principle antimalarial agents, metacycloprodigiosin, bafilomycin A1, and spectinabilin. Metacycloprodigiosin exhibited potent in vitro activity against Plasmodium falciparum K1, with a 50% inhibitory concentration of 0.0050 ± 0.0010 μg/ml, while its cytotoxicity was much weaker.

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Prenylated Isoflavanones from the Stem Bark of Erythrina poeppigiana (Leguminosae) and its Antimalarial Properties

Natural Product Communications ◽

10.1177/1934578x1701200825 ◽

2017 ◽

Vol 12 (8) ◽

pp. 1934578X1701200 ◽

Cited By ~ 1

Author(s):

Tati Herlina ◽

Anderson Arnold Aloanis ◽

Dikdik Kurnia ◽

Desi Harneti ◽

Rani Maharani ◽

...

Keyword(s):

Methanol Extract ◽

Ethyl Acetate Extract ◽

Antimalarial Activity ◽

Stem Bark ◽

In Vitro Bioassay ◽

Erythrina Poeppigiana ◽

Antimalarial Agents ◽

Bioassay Guided Fractionation ◽

Promising Source

During the course of our continuous search for novel antimalarial compounds derived from the Indonesian Erythrina plants, the methanol extract of the stem bark of Erythrina poeppigiana demonstrated significant antimalarial activity against Plasmodium falciparum parasites, in vitro. Bioassay-guided fractionation of the ethyl acetate extract resulted in the isolation of three known platyisoflavanone (1), erypogein D (2), and sophoraisoflavanone A (3). Compounds 1–3 showed strong antimalarial activity against 3D7 strain of P. falciparum with IC50 values of 0.52, 0.36, and 3.65μM, respectively. This result indicates that stem bark of E. poeppigiana is a promising source of antimalarial agents, and merits further investigation.

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Antipoliovirus Activity of the Organic Extract ofEupatorium buniifolium: Isolation of Euparin as an Active Compound

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/402364 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

María Florencia Visintini Jaime ◽

Rodolfo H. Campos ◽

Virginia S. Martino ◽

Lucía V. Cavallaro ◽

Liliana V. Muschietti

Keyword(s):

Antiviral Activity ◽

Vero Cells ◽

Replication Cycle ◽

Active Principle ◽

Organic Extract ◽

Plaque Reduction Assay ◽

Virus Adsorption ◽

Bioassay Guided Fractionation

The antiviral activity of the organic extract (OE) ofEupatorium buniifoliumagainst poliovirus type 1 was determined byin vitroassays with an effective concentration 50 (EC50) of 23.3 ± 3.3 µg/mL. Bioassay-guided fractionation of the OE allowed the isolation of an active principle that was identified by spectroscopic methods (1H- and13C-NMR, EI-MS, UV, and IR spectroscopy) as the benzofuran euparin. The plaque reduction assay in Vero cells was used to assess the antiviral activity of euparin against poliovirus types 1, 2, and 3 with EC50values of 0.47, 0.12, and 0.15 µg/mL, respectively. Moreover, this compound showed high selectivity indexes of 284.9, 1068, and 854.7, respectively. In order to identify the mechanism by which euparin exerts its antiviral activity, the virucidal effect, the pretreatment of Vero cells, and the time of action on one viral replication cycle were evaluated. Results obtained demonstrated that euparin exerts its effect during the early events of the replication cycle, from the virus adsorption to cells up to the first twenty minutes after infection. This is the first report on the presence of euparin inE. buniifoliumand its antiviral activity.

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Synthesis, Antimalarial Evaluation and SAR Study of Some 1,3,5-Trisubstituted Pyrazoline Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178616666190212145754 ◽

2019 ◽

Vol 16 (10) ◽

pp. 807-817 ◽

Cited By ~ 1

Author(s):

Shilpy Aggarwal ◽

Deepika Paliwal ◽

Dhirender Kaushik ◽

Girish Kumar Gupta ◽

Ajay Kumar

Keyword(s):

Antimalarial Activity ◽

Analysis Data ◽

Docking Study ◽

Maximum Activity ◽

Elemental Analysis Data ◽

Mass Spectral ◽

Structure Activity ◽

Pharmacokinetic Properties ◽

Sar Study

The synthesis of a novel series of 1,3,5-trisubstitiuted pyrazoline was achieved by refluxing chalcone derivative with different heteroaryl hydrazines. The newly synthesized compounds were characterized by 1H NMR, 13CNMR, mass spectral and elemental analysis data. The synthetic series of novel pyrazoline hybrids was screened for in vitro schizont maturation assay against chloroquine sensitive 3D7 strain of Plasmodium falciparum. Most of the compounds showed promising in vitro antimalarial activity against CQ sensitive strain. The preliminary structure-activity relationship study showed that quinoline substituted analog at position N-1 showed maximum activity followed by benzothiazole substitution, while phenyl substitution lowers the antimalarial activity. The observed activity was persistent by the docking study on P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.

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Discovery of 3-Cinnamamido-N-Substituted Benzamides as Potential Antimalarial Agents

Medicinal Chemistry ◽

10.2174/1573406416666200817160708 ◽

2020 ◽

Vol 16 ◽

Author(s):

Haicheng Liu ◽

Yushi Futamura ◽

Honghai Wu ◽

Aki Ishiyama ◽

Taotao Zhang ◽

...

Keyword(s):

Mammalian Cells ◽

Antimalarial Activity ◽

In Vitro Assays ◽

Compound Library ◽

Antimalarial Agents ◽

Phenotypic Screen ◽

Ic50 Values ◽

Substituted Benzamides

Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3-cinnamamido-N-substituted benzamides. Method: In this study, a screening of our compound library was carried out against the multidrug-sensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 µM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 µM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, phenotypic screen of our compound library resulted in the first report of 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against P. falciparum 3D7 strain with IC50 values around 0.1 µM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.

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

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

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.

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In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2094 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2094-2098 ◽

Cited By ~ 13

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.

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Bio-Guided Isolation of Antimalarial Metabolites from the Coculture of Two Red Sea Sponge-Derived Actinokineospora and Rhodococcus spp.

Marine Drugs ◽

10.3390/md19020109 ◽

2021 ◽

Vol 19 (2) ◽

pp. 109

Author(s):

Hani A. Alhadrami ◽

Bathini Thissera ◽

Marwa H. A. Hassan ◽

Fathy A. Behery ◽

Che Julius Ngwa ◽

...

Keyword(s):

Red Sea ◽

Antimalarial Activity ◽

Axenic Culture ◽

Trna Synthetase ◽

Structural Motif ◽

Natural Habitats ◽

Signalling Molecules ◽

Chemical Signalling ◽

Axenic Conditions

Coculture is a productive technique to trigger microbes’ biosynthetic capacity by mimicking the natural habitats’ features principally by competition for food and space and interspecies cross-talks. Mixed cultivation of two Red Sea-derived actinobacteria, Actinokineospora spheciospongiae strain EG49 and Rhodococcus sp. UR59, resulted in the induction of several non-traced metabolites in their axenic cultures, which were detected using LC–HRMS metabolomics analysis. Antimalarial guided isolation of the cocultured fermentation led to the isolation of the angucyclines actinosporins E (1), H (2), G (3), tetragulol (5) and the anthraquinone capillasterquinone B (6), which were not reported under axenic conditions. Interestingly, actinosporins were previously induced when the axenic culture of the Actinokineospora spheciospongiae strain EG49 was treated with signalling molecule N-acetyl-d-glucosamine (GluNAc); this finding confirmed the effectiveness of coculture in the discovery of microbial metabolites yet to be discovered in the axenic fermentation with the potential that could be comparable to adding chemical signalling molecules in the fermentation flask. The isolated angucycline and anthraquinone compounds exhibited in vitro antimalarial activity and good biding affinity against lysyl-tRNA synthetase (PfKRS1), highlighting their potential developability as new antimalarial structural motif.

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