scholarly journals Evaluation of a Series of 9,10-Anthraquinones as Antiplasmodial Agents

2019 ◽  
Vol 16 (3) ◽  
pp. 353-363 ◽  
Author(s):  
Che Puteh Osman ◽  
Nor Hadiani Ismail ◽  
Aty Widyawaruyanti ◽  
Syahrul Imran ◽  
Lidya Tumewu ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Hydrophobic Interactions ◽  
Structural Characteristics ◽  
Structural Features ◽  
Antiplasmodial Activity ◽  
Hydroxyl Groups ◽  
Phytochemical Study ◽  
Methyl Group ◽  
Ic50 Value

Background: A phytochemical study on medicinal plants used for the treatment of fever and malaria in Africa yielded metabolites with potential antiplasmodial activity, many of which are Anthraquinones (AQ). AQs have similar sub-structure as naphthoquinones and xanthones, which were previously reported as novel antiplasmodial agents. </P><P> Objective: The present study aimed to investigate the structural requirements of 9,10- anthraquinones with hydroxy, methoxy and methyl substituents to exert strong antiplasmodial activity and to investigate their possible mode of action. </P><P> Methods: Thirty-one AQs were synthesized through Friedel-Crafts reaction and assayed for antiplasmodial activity in vitro against Plasmodium falciparum (3D7). The selected compounds were tested for toxicity and probed for their mode of action against β-hematin dimerization through HRP2 and lipid catalyses. The most active compounds were subjected to a docking study using AutoDock 4.2. </P><P> Results: The active AQs have similar common structural characteristics. However, it is difficult to establish a structure-activity relationship as certain compounds are active despite the absence of the structural features exhibited by other active AQs. They have either ortho- or meta-arranged substituents and one free hydroxyl and/or carbonyl groups. When C-6 is substituted with a methyl group, the activity of AQs generally increased. 1,3-DihydroxyAQ (15) showed good antiplasmodial activity with an IC50 value of 1.08 &#181;M, and when C-6 was substituted with a methyl group, 1,3- dihydroxy-6-methylAQ (24) showed stronger antiplasmodial activity with an IC50 value of 0.02 &#181;M, with better selectivity index. Compounds 15 and 24 showed strong HRP2 activity and mild toxicity against hepatocyte cells. Molecular docking studies showed that the hydroxyl groups at the ortho (23) and meta (24) positions are able to form hydrogen bonds with heme, of 3.49 Å and 3.02 Å, respectively. </P><P> Conclusion: The activity of 1,3-dihydroxy-6-methylAQ (24) could be due to their inhibition against the free heme dimerization by inhibiting the HRP2 protein. It was further observed that the anthraquinone moiety of compound 24 bind in parallel to the heme ring through hydrophobic interactions, thus preventing crystallization of heme into hemozoin.

scholarly journals Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4116
Author(s):  
Sheila C. Araujo ◽  
Fernanda S. Sousa ◽  
Thais A. Costa-Silva ◽  
Andre G. Tempone ◽  
João Henrique G. Lago ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Response ◽  
Structural Features ◽  
New Drugs ◽  
In Vitro Assays ◽  
Computational Techniques ◽  
Phytochemical Study ◽  
Ic50 Value ◽  
In Silico Studies

In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC50 value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC50 > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD.

scholarly journals Ellagic Acid Derivatives from Syzygium cumini Stem Bark: Investigation of their Antiplasmodial Activity

2009 ◽  
Vol 4 (10) ◽  
pp. 1934578X0900401 ◽  
Author(s):  
Claudia A. Simões-Pires ◽  
Sandra Vargas ◽  
Andrew Marston ◽  
Jean-Robert Ioset ◽  
Marçal Q. Paulo ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ellagic Acid ◽  
Stem Bark ◽  
Antimalarial Drugs ◽  
Antiplasmodial Activity ◽  
Hydroxyl Groups ◽  
Syzygium Cumini ◽  
Free Hydroxyl ◽  
Ellagic Acid Derivatives

Bioguided fractionation of Syzygium cumini (Myrtaceae) bark decoction for antiplasmodial activity was performed, leading to the isolation of three known ellagic acid derivatives (ellagic acid, ellagic acid 4-O-α-L-2″-acetylrhamnopyranoside, 3-O-methylellagic acid 3′-O-α-L-rhamnopyranoside), as well as the new derivative 3-O-methylellagic acid 3′-O-β-D-glucopyranoside. Activity investigation was based on the reduction of P. falciparum (PfK1) parasitaemia in vitro and the inhibition of β-hematin formation, a known mechanism of action of some antimalarial drugs. Among the investigated ellagic acid derivatives, only ellagic acid was able to reduce P. falciparum parasitaemia in vitro and inhibit β-hematin formation, suggesting that free hydroxyl groups are necessary for activity within this class of compounds.

scholarly journals Chemical Composition and In Vitro Antiplasmodial Activity of the Ethanolic Extract of Cyperus articulatus var. nodosus Residue

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 889
Author(s):  
Francisco Flávio Vieira de Assis ◽  
Nazaré Carneiro da Silva ◽  
Waldiney Pires Moraes ◽  
Lauro Euclides Soares Barata ◽  
Antonio Humberto Hamad Minervino
Keyword(s):  
Inhibitory Concentration ◽  
Therapeutic Potential ◽  
Low Cost ◽  
Ethanolic Extract ◽  
Antiplasmodial Activity ◽  
Solid Residue ◽  
Phytochemical Study ◽  
Commercial Purpose ◽  
Cytotoxicity Activities

Cyperus articulatus L. is popularly known as priprioca. Its rhizomes are used as a medicine in the treatment of malaria in traditional medicine. Since priprioca oil is extracted for commercial purpose, we evaluated if the components from the priprioca residue can be a source of antiplasmodial active molecules. This study aimed to determine the in vitro antiplasmodial and cytotoxicity activities of the ethanolic extract of C. articulatus as an in vitro antiplasmodial agent. From the solid residue of the plant rhizomes, 40 g samples were removed and subjected to hot extraction using a Soxhlet extractor. The in vitro antiplasmodial activity was determined using the W2 and 3D7 strains of P. falciparum. The phytochemical study identified the following main compounds: corymbolone (14.25%), cyclocolorenone (9.75%), and cadalene (8.36%). The extract exhibited moderate IC50 (inhibitory concentration) against the two strains of P. falciparum: 1.21 ± 0.01 against the W2 strain and 1.10 ± 0.06 µg/mL against the 3D7 strain. Our results show the therapeutic potential of priprioca residue as a low-cost antiplasmodial agent.

scholarly journals Aroma Profile of Star Anise and the Structure-odor Relationship of Anethole

2014 ◽  
Vol 9 (2) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Toshio Hasegawa ◽  
Haruna Seimiya ◽  
Takashi Fujihara ◽  
Noriko Fujiwara ◽  
Hideo Yamada
Keyword(s):  
Hydrogen Atom ◽  
Methoxy Group ◽  
Structural Characteristics ◽  
Structural Features ◽  
Aroma Profile ◽  
Methyl Group ◽  
Star Anise ◽  
Main Component ◽  
Relationship Of ◽  
Methyl Benzene

Star anise is an important fragrance material that has a characteristic anise-like odor. Although the main component of star anise is ( E)-anethole, which accounts for over 90% of the constituents, the odor of ( E)-anethole is different from that of the material itself. Here, we examined the aroma profile of star anise. GC-MS analysis of star anise extracts showed that it contains many compounds with structures similar to ( E)-anethole. Our results indicate that ( E)-anethole is the key compound in the odor of star anise, but structurally similar compounds play an important role in creating its odor. We examined the structure-odor relationship of ( E)-anethole, focusing on the methoxy and 1-propenyl substituents. Altering the 1-propenyl group changed the odors of all the anethole derivatives. Replacing the methoxy group with a hydrogen atom created compounds with similar fatty odors. This shows that the methoxy group is important for the characteristic odor of anethole. We synthesized anethole derivatives where the methoxy group was replaced with a methyl group. In both methoxy- and methyl-substituted anethole derivatives, altering the 1-propenyl group changed the odors of the derivatives. Therefore, the methoxy and methyl benzene moieties are important structural features for the odor of star anise. The structural characteristics of anethole are closely related to its odor expression.

scholarly journals Antioxidant and Antidiabetic Effects of Flavonoids: A Structure-Activity Relationship Based Study

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Murni Nazira Sarian ◽  
Qamar Uddin Ahmed ◽  
Siti Zaiton Mat So’ad ◽  
Alhassan Muhammad Alhassan ◽  
Suganya Murugesu ◽  
...  
Keyword(s):  
Radical Scavenging ◽  
Structural Features ◽  
Biochemical Properties ◽  
Hydroxyl Groups ◽  
Dpph Radical ◽  
Dot Blot ◽  
Antioxidant Power ◽  
Dipeptidyl Peptidase 4 ◽  
Ferric Reducing Antioxidant Power

The best described pharmacological property of flavonoids is their capacity to act as potent antioxidant that has been reported to play an important role in the alleviation of diabetes mellitus. Flavonoids biochemical properties are structure dependent; however, they are yet to be thoroughly understood. Hence, the main aim of this work was to investigate the antioxidant and antidiabetic properties of some structurally related flavonoids to identify key positions responsible, their correlation, and the effect of methylation and acetylation on the same properties. Antioxidant potential was evaluated through dot blot, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ABTS+radical scavenging, ferric reducing antioxidant power (FRAP), and xanthine oxidase inhibitory (XOI) assays. Antidiabetic effect was investigated throughα-glucosidase and dipeptidyl peptidase-4 (DPP-4) assays. Results showed that the total number and the configuration of hydroxyl groups played an important role in regulating antioxidant and antidiabetic properties in scavenging DPPH radical, ABTS+radical, and FRAP assays and improved bothα-glucosidase and DPP-4 activities. Presence of C-2-C-3 double bond and C-4 ketonic group are two essential structural features in the bioactivity of flavonoids especially for antidiabetic property. Methylation and acetylation of hydroxyl groups were found to diminish thein vitroantioxidant and antidiabetic properties of the flavonoids.

Antiplasmodial activity of faloak bark (Sterculia quadrifida, R.Br.) extract from East Nusa Tenggara, Indonesia

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Priska Ernestina Tenda ◽  
Maria Hilaria ◽  
Arba Pramundita Ramadani
Keyword(s):  
Antimalarial Activity ◽  
Ethanolic Extract ◽  
Antiplasmodial Activity ◽  
Current Development ◽  
Antimalarial Drug Resistance ◽  
Falciparum Strain ◽  
Ic50 Value ◽  
Endemic Medicinal Plant ◽  
The Relationship

The current development of antimalarial drug resistance encourages researchers to discover  and develop novel antimalarials. One of its alternatives for antimalarial discovery is using medicinal plants remembering the success of artemisinin. Sterculia quardrifida R. Br. bark, locally name as faloak, is an endemic medicinal plant from East Nusa Tenggara that has been used traditionally to treat malaria. However, its antimalarial activity has not been investigated, yet. This study was aimed to evaluate the antiplasmodial activity of ethanolic extract of faloak bark against Plasmodium falciparum in vitro. Using FCR-3 P. falciparum strain, the ethanolic extract was evaluated on various concentration (1, 10, 50, and 100 μg/mL, respectively). The IC50 value was determined by the relationship between concentration and percentage of growth inhibition. The result showed that the percentage of inhibition of P. falciparum was concentration dependent, higher concentration resulting on higher percentage of inhibition with the IC50 42.399 ± 9.517 μg/mL. It can be concluded that the ethanolic extract of faloak bark have moderate antiplasmodial activity against P. falciparum in vitro.

scholarly journals Compounds Structurally Related to Ellagic Acid Show Improved Antiplasmodial Activity

2008 ◽  
Vol 53 (2) ◽  
pp. 622-630 ◽  
Author(s):  
Nicole Sturm ◽  
Ying Hu ◽  
Herbert Zimmermann ◽  
Karin Fritz-Wolf ◽  
Sergio Wittlin ◽  
...  
Keyword(s):  
Ellagic Acid ◽  
A549 Cells ◽  
Antiplasmodial Activity ◽  
In Vivo Studies ◽  
Hydroxyl Groups ◽  
Redox Enzymes ◽  
Trophozoite Stage ◽  
Antioxidant Genes ◽  
Nanomolar Range

ABSTRACT The cancer chemopreventive agent ellagic acid (EA) is a known inhibitor of glutathione S-transferases (GSTs) and possesses antiplasmodial activities in the upper-nanomolar range. In the recent drug development approach, the properties of the active site of Plasmodium falciparum GST were exploited for inhibitor design by introducing one or two additional hydroxyl groups into EA, yielding flavellagic acid (FEA) and coruleoellagic acid (CEA), respectively. Indeed, the inhibition of P. falciparum GST was improved with the increasing hydrophilicity of the planar polyaromatic ring system. Studying the effects of the two compounds on the central redox enzymes of Plasmodium revealed that glutathione reductase and thioredoxin reductase also are inhibited in the lower-micromolar range. Both compounds had strong antiplasmodial activity in the lower-nanomolar range and were particularly effective against chloroquine (CQ)-resistant P. falciparum strains. Neither FEA nor CEA showed cytotoxic effects on human cells. This was supported by negligible changes in transcript levels and enzyme activities of redox enzymes in human A549 cells upon treatment with the compounds. In Plasmodium, however, CEA treatment resulted in a marked downregulation of most antioxidant genes studied and impaired mainly the trophozoite stage of the parasites. In addition, EA, CEA, and FEA were found to strongly inhibit in vitro heme aggregation. In vitro and preliminary in vivo studies indicated that, compared to CQ, CEA is a slowly acting compound and is able to significantly improve the survival of Plasmodium berghei-infected mice. We conclude that FEA and CEA are promising antimalarial compounds that deserve to be studied further.

Synthesis and Antiplasmodial Activity of 4-Alkylidene(arylidene)hydrazono-1,3-oxazinan-2-ones and 3-Hydroxy-N'-alkylidene(arylidene)propanehydrazonamides

2010 ◽  
Vol 63 (10) ◽  
pp. 1430 ◽  
Author(s):  
Mehdi Khankischpur ◽  
Rolf D. Walter ◽  
Thomas Kurz
Keyword(s):  
Plasmodium Falciparum ◽  
Sensitive Strain ◽  
Antiplasmodial Activity ◽  
Ic50 Value

Previously unreported 6-substituted 4-alkylidene(arylidene)hydrazono-1,3-oxazinan-2-ones and a series of open-chained 3-hydroxy-N′-alkylidene(arylidene)propanehydrazonamides were synthesized and evaluated for their in vitro antiplasmodial activity. The most active 3-hydroxy-N′-alkylidene(arylidene)propanehydrazonamide exhibits potent in vitro antiplasmodial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum and demonstrates an IC50 value of 0.2 µM.

scholarly journals SYNTHESIS OF 4-HYDROXY-3-(1-HYDROXY-2-(SUBSTITUTEDAMINO)ETHYL)-1-PHENYL/ METHYL QUINOLIN-2(1H)-ONE AS ANTICANCER AGENTS

2017 ◽  
Vol 10 (8) ◽  
pp. 225
Author(s):  
Prachi Bajaj ◽  
Shivlingrao Mamle Desai ◽  
Pearl Dighe ◽  
Soniya Naik ◽  
Bheemanagouda Biradar
Keyword(s):  
Anticancer Agents ◽  
Hydroxyl Group ◽  
Primary Amines ◽  
Moderate Activity ◽  
Mass Spectral Data ◽  
Methyl Group ◽  
Mass Spectral ◽  
Cyclic Amines ◽  
Ic50 Value

  Objective: The current work is concerned with the synthesis of a series of 4-hydroxy-3-(1-hydroxy-2-(substituted amino)ethyl)-1-phenyl/ methylquinolin-2(1H)-one[III-a(1-5)/III-b(1-5)] and evaluation of its in vitro anticancer activity.Methods: The starting material for linomide analogs was synthesized by following literature procedures. The carbonyl group was reduced to hydroxyl group using sodium borohydride, and the methyl group was brominated using bromine in acetic acid. Further bromine was nucleophilically substituted by primary amines. All the synthesized compounds were satisfactorily characterized by infrared, nuclear magnetic resonance, and mass spectral data. The synthesized compounds were tested for in vitro anticancer activity against MDA-MB cell line using the MTT assay method.Results: Among all the synthesized compounds, compound [III-a1;R=C6H5,R1=n-propylamine], [III-b1;R=CH3,R1=n-propylamine], and [III-b2;R=CH3,R1=methylamine] were found to be most cytotoxic with IC50 value=25 μg against the MDA-MB cell line.Conclusion: The results of screening studies concluded that compounds with (C6H5 at C1) and (long chain aliphatic and cyclic amines at C3) position of quinolin-2-one ring showed moderate activity.

scholarly journals THE EFFECT OF MALACCA LEAVES (Phyllantus emblica) ETHANOLIC EXTRACT ON Plasmodium falciparum GROWTH IN VITRO

2018 ◽  
Vol 12 (4) ◽  
Author(s):  
Nuzul Asmilia ◽  
T Armansyah TR ◽  
Dwinna Aliza ◽  
Juli Melia ◽  
Erdiansyah Rahmi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Ethanolic Extract ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Probit Analysis ◽  
Antiplasmodial Activity ◽  
Control Group ◽  
Ic50 Value

The aim of this research was to find out in vitro antiplasmodium activity of Malacca leaves (Phyllantus emblica) ethanolic extract against Plasmodium falciparum growth. In this study, Plasmodium culture contained 5% parasitemia in ring stage was cultured using candle jar method and antiplasmodial activity test was carried out using microculture. The treatments were divided into 7 groups with four repetitions. K1 as negative control group was given Roswell Park Memorial Institute (RPMI), while K2 as positive control group was given artesdiaquine. Groups K3, K4, K5, K6, and K7 group was added with 100 µg/mL, 75 µg/mL, 50 µg/mL, 25 µg/mL, and 5 µg/mL of Malacca leaves ethanolic extract, respectively. Antiplasmodial activity was determined by inhibition concentration of 50% parasite growth (IC50). The data were analyzed using ANOVA and followed by Duncan test. The average of parasitemia level in group K1, K2, K3, K4, K5, K6, and K7 were 55.25±15.62, 8.50±2.52, 8.50±3.00, 9.25±0.95, 9.00±2.70, 9.79±2.06, and 10.75±2.22, respectively. The average of inhibition percentage in group K1, K2; K3; K4; K5; K6; and K7 were 0.00±0.00%, 84.62±4.55%; 84.62±5.43%; 83.26±1.73%; 83.71±4,90%; 82.35±3,73%; and 80.54±6.83%, respectively (P0.01). The results showed that the administration of malacca leaves ethanolic extract significantly affect (P0.01) the inhibition of Plasmodium growth as compared to group K1 (negative control). Probit analysis reveals the IC50 value was 3.889 µg/mL. In conclusion, all doses of malacca leaves ethanolic extract used in this study was able to inhibit Plasmodium falciparum growth with IC50 value was 3.889 µg/mL.

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