scholarly journals SAR and pharmacophore models for the rhodanine inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase

IUBMB Life ◽  
2010 ◽  
Vol 62 (3) ◽  
pp. 204-213 ◽  
Author(s):  
Gyanendra Kumar ◽  
Tanushree Banerjee ◽  
Neha Kapoor ◽  
Namita Surolia ◽  
Avadhesha Surolia
Keyword(s):  
Plasmodium Falciparum ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Pharmacophore Models

scholarly journals IN-SILICO SCREENING AGAINST ANTIMALARIAL TARGET PLASMODIUM FALCIPARUM ENOYL-ACYL CARRIER PROTEIN REDUCTASE

2017 ◽  
Vol 10 (17) ◽  
pp. 127
Author(s):  
Berwi Fazri Pamudi ◽  
Azizahwati Azizahwati ◽  
Arry Yanuar
Keyword(s):  
Plasmodium Falciparum ◽  
Virtual Screening ◽  
In Silico ◽  
Acyl Carrier Protein ◽  
Parasitic Infection ◽  
Antimalarial Drugs ◽  
Chemotherapeutic Agents ◽  
Effective Vaccine ◽  
Carrier Protein ◽  
In Silico Screening

  Objective: Malaria is a parasitic infection that causes worldwide health problems. The absence of an effective vaccine and Plasmodium strains that are resistant to antimalarial drugs emphasize the importance of developing new chemotherapeutic agents. The use of computers for in-silico screening, or virtual screening, is currently being developed as a method for discovering antimalarial drugs. One of the enzymes that can support the development of the malaria parasite is the Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR). Inhibition of these enzymes leads to Type II lipid biosynthesis inhibition on the parasite.Methods: This research investigates the use of virtual screening to find PfENR inhibitor candidates. A molecular docking method using GOLD software and the medicinal plants in Indonesia database will be used. This target has been optimized by the removal of residues and the addition of charge. Ligand is expected to be an inhibitor of PfENR.Results: In-silico screening, or virtual screening, found that the top five compounds with the highest GOLD score at trial are kaempferol 3-rhamnosyl- (1-3)-rhamnosyl-(1-6)-glucoside; cyanidin 3,5-di-(6-malonylglucoside); 8-hydroxyapigenin 8-(2’’, 4’’-disulfato glucuronide); epigallocatechin 3,5,-di- O-gallat; quercetin 3,4’-dimethyl ether 7-alpha-L-arabinofuranosyl-(1-6)-glucoside. They had GOLD scores of 94.73, 95.90, 86.46, 85.39, and 84.40, respectively.Conclusions: There are two candidate inhibitor compounds from tea (Camellia sinensis), which have potential for development as an antimalarial drug, which are kaempferol 3-rhamnosyl-(1-3)-rhamnosyl-(1-6)-glucoside and epigallocatechin 3,5,-di-O-gallate, with a GOLD score of 94.73 and 85.39, respectively.

Structural basis for the functional and inhibitory mechanisms of β-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Plasmodium falciparum

2011 ◽  
Vol 176 (2) ◽  
pp. 238-249 ◽  
Author(s):  
Koustav Maity ◽  
Bharat Somireddy Venkata ◽  
Neha Kapoor ◽  
Namita Surolia ◽  
Avadhesha Surolia ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Acyl Carrier Protein ◽  
Structural Basis ◽  
Carrier Protein ◽  
Inhibitory Mechanisms

scholarly journals Analysis Docking Of Plasmodium Falciparum Enoyl Acyl Carrier Protein Reductase (Pfenr) With Organic Compunds From Virtual Screening Of Herbal Database

2020 ◽  
Vol 3 (1) ◽  
pp. 127
Author(s):  
Nya Daniaty Malau ◽  
St Fatimah Azzahra
Keyword(s):  
Plasmodium Falciparum ◽  
Virtual Screening ◽  
In Silico ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Chemotherapeutic Agents ◽  
Effective Vaccine ◽  
Carrier Protein ◽  
Autodock Vina ◽  
In Silico Screening

Malaria is one of problematic infectious diseases worldwide. The absence of an effective vaccine and the spread of drug resistant strains of Plasmodium clearly indicate the necessity for the deveploment of new chemotherapeutic agents. Recent method being developed is searching a new drug of antimalarial using in silico screening, or also known as virtual screening. One of enzyme target that important for growth of the malaria parasite is Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR). Inhibition of this enzyme cause the fatty acid biosynthesis type II will be terminated. In this research, in silico screening was performed using AUTODOCK VINA software to find inhibitor candidates of PfENR by using ligands from the database of Medicinal Plants in Indonesia. On the AUTODOCK VINA software moleculer docking experiments were performed between ligands and macromolecule target PfENR. This target that has been optimized with residue removal and charges addition. Ligand is expected to be the PfENR inhibitors.

Virtually Designed Triclosan-Based Inhibitors of Enoyl-Acyl Carrier Protein Reductase of Mycobacterium tuberculosis and of Plasmodium falciparum

2015 ◽  
Vol 34 (5) ◽  
pp. 292-307 ◽  
Author(s):  
Luc C. Owono Owono ◽  
Fidele Ntie-Kang ◽  
Melalie Keita ◽  
Eugene Megnassan ◽  
Vladimir Frecer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mycobacterium Tuberculosis ◽  
Acyl Carrier Protein ◽  
Carrier Protein

scholarly journals Kinetic, inhibition and structural studies on 3-oxoacyl-ACP reductase from Plasmodium falciparum, a key enzyme in fatty acid biosynthesis

2005 ◽  
Vol 393 (2) ◽  
pp. 447-457 ◽  
Author(s):  
Sasala R. Wickramasinghe ◽  
Kirstine A. Inglis ◽  
Jonathan E. Urch ◽  
Sylke Müller ◽  
Daan M. F. van Aalten ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Plasmodium Falciparum ◽  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Competitive Inhibition ◽  
Acyl Carrier Protein ◽  
Antimalarial Activity ◽  
Kinetic Properties ◽  
Carrier Protein ◽  
Acid Biosynthesis

Type II fatty acid biosynthesis represents an attractive target for the discovery of new antimalarial drugs. Previous studies have identified malarial ENR (enoyl acyl-carrier-protein reductase, or FabI) as the target for the antiseptic triclosan. In the present paper, we report the biochemical properties and 1.5 Å (1 Å=0.1 nm) crystal structure of OAR (3-oxoacyl acyl-carrier-protein reductase, or FabG), the second reductive step in fatty acid biosynthesis and its inhibition by hexachlorophene. Under optimal conditions of pH and ionic strength, Plasmodium falciparum OAR displays kinetic properties similar to those of OAR from bacteria or plants. Activity with NADH is <3% of that with NADPH. Fluorescence enhancement studies indicate that NADPH can bind to the free enzyme, consistent with kinetic and product inhibition studies suggesting a steady-state ordered mechanism. The crystal structure reveals a tetramer with a sulphate ion bound in the cofactor-binding site such that the side chains of the catalytic triad of serine, tyrosine and lysine are aligned in an active conformation, as previously observed in the Escherichia coli OAR–NADP+ complex. A cluster of positively charged residues is positioned at the entrance to the active site, consistent with the proposed recognition site for the physiological substrate (3-oxoacyl-acyl-carrier protein) in E. coli OAR. The antibacterial and anthelminthic agent hexachlorophene is a potent inhibitor of OAR (IC50 2.05 μM) displaying non-linear competitive inhibition with respect to NADPH. Hexachlorophene (EC50 6.2 μM) and analogues such as bithionol also have antimalarial activity in vitro, suggesting they might be useful leads for further development.

scholarly journals The Effect of Thespesia populnea Against Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase Receptor by Study In Silico

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
I Made Prasetya Kurniawan ◽  
Prawesty Diah Utami ◽  
Risma Risma
Keyword(s):  
Plasmodium Falciparum ◽  
Active Compound ◽  
In Silico ◽  
Acyl Carrier Protein ◽  
Carrier Protein ◽  
Active Compounds ◽  
Prediction Analysis ◽  
Thespesia Populnea ◽  
Study Results ◽  
In Silico Studies

Indonesia is a country that has abundant natural resources; one of them is the Baru laut plant which is the latest breakthrough because it has an active substance that can be used as an anti-malaria medicine. It is very beneficial because there has been a case of resistance of artemisinin derivatives in Indonesia. The purpose of this study was to determine the potential of active compounds in Baru laut plants (Thespesia populnea (L.) Soland ex. Correa) against the Plasmodium falciparum enoyl acyl carrier protein reductase receptor in P. falciparum through in silico studies. This research is purely experimental using the One-Shot Experimental Study research design method. Observations were only made once between the variables studied through three analyzes, namely prediction analysis of active compound content, prediction analysis of the mechanism of action of active compound content, and prediction analysis of ADME active compound. The study results show that there are three active compounds in Baru laut plants that have antimalarial potential. The three compounds include gossypol, linoleic acid, and beta-sitosterol, have their respective potential in becoming a malaria drug. This study concludes that Baru laut plants have potential as anti-malaria drugs.

scholarly journals Discovery of novel inhibitors targeting enoyl–acyl carrier protein reductase in Plasmodium falciparum by structure-based virtual screening

2007 ◽  
Vol 358 (3) ◽  
pp. 686-691 ◽  
Author(s):  
George Nicola ◽  
Colin A. Smith ◽  
Edinson Lucumi ◽  
Mack R. Kuo ◽  
Luchezar Karagyozov ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Virtual Screening ◽  
Acyl Carrier Protein ◽  
Carrier Protein
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