scholarly journals DOCKING STUDIES OF AMINOHYDANTOIN DERIVATIVES AS ANTIMALARIAL AGENTS

2018 ◽  
Vol 8 (5-s) ◽  
pp. 322-326
Author(s):  
Pooja Mali ◽  
Shourya Pratap ◽  
Raghvendra S. Badhauria ◽  
Himanshu Gurjar
Keyword(s):  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Site ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Interaction ◽  
Antimalarial Agents ◽  
Rank Score ◽  
Observable Data ◽  
Virtual Platform

Objective: Docking studies of aminohydantoin derivatives as antimalarial agents. A novel derivative of aminohydantoins was selected from the literature. Method: in-silco studies using docking methodology. The compounds were sketched and energy minimized using Chem draw ultra and Chem 3D ultra respectively. Further, the compounds were docked into Plasmodium falciparum transferase inhibitor (3L7) using Molegro Virtual Platform. Twenty eight compounds were docked into the active site of Pf-lactate dehydrogenase cavity and all of them found to have similar binding interactions of a co-crystalized ligand. Result: The compounds were showed good docking score like moldock score and re-rank score. The finding of docking studies shows a typical molecular interaction pattern with lactate dehydrogenase. The binding interaction information derived from these molecules will be useful in future antimalarial agent design. Conclusion: From the docking study, it was observed that ligands bind to the electrostatic, hydrophobic clamp formed by the residues Asp 76(B), Tyr 190(B), Tyr 80(B) and Lys 72(B) which play an important role for Plasmodium falciparum inhibition.   The binding affinity, grid calculation and RMSD percentage lower and upper   parameters were calculated.   Hence, the observable data indicated that, above compounds can serve as good leads for further modification and optimization in the of treatment malaria. Keywords: Molegro, Chemdraw, aminohydantoins and docking, studies as Plasmodium falciparum, 4RAO, moldock score.

scholarly journals Antimalarial Activity of Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme Selected by Docking Studies

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e21237 ◽  
Author(s):  
Julia Penna-Coutinho ◽  
Wilian Augusto Cortopassi ◽  
Aline Alves Oliveira ◽  
Tanos Celmar Costa França ◽  
Antoniana Ursine Krettli
Keyword(s):  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Antimalarial Activity ◽  
Docking Studies ◽  
Dehydrogenase Enzyme ◽  
Potential Inhibitors

scholarly journals Functional and structural resilience of the active site loop in the evolution of Plasmodium lactate dehydrogenase

2018 ◽  
Author(s):  
Jacob D. Wirth ◽  
Jeffrey I. Boucher ◽  
Joseph R. Jacobowitz ◽  
Scott Classen ◽  
Douglas L. Theobald
Keyword(s):  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Malate Dehydrogenase ◽  
Active Site ◽  
Drug Target ◽  
Insertion Sequence ◽  
High Potential ◽  
Ldh Activity

AbstractThe malarial pathogen Plasmodium falciparum (Pf) is a member of the Apicomplexa, which independently evolved a highly specific lactate dehydrogenase (LDH) from an ancestral malate dehydrogenase (MDH) via a five-residue insertion in a key active site loop. PfLDH is widely considered an attractive drug target due to its unique active site. Apicomplexan loop conservation suggests that a particular insertion sequence was required to evolve LDH specificity, and we previously showed (Boucher 2014) that a tryptophan in the insertion, W107f, is essential for activity and specificity. However, the roles of other residues in the loop are currently unknown. Here we show that PfLDH activity is remarkably resilient to radical perturbations of both loop identity and length. Thus, alternative insertions could have evolved LDH specificity as long as they contained a tryptophan in the proper location. PfLDH therefore has high potential to develop resistance to drugs that target its distinctive active site.

scholarly journals In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Harvijay Singh
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Viral Infections ◽  
Drug Repurposing ◽  
Docking Study ◽  
Docking Studies ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

scholarly journals Synthesis, Molecular Docking, and Evaluation of Some New Curcumin Analogs as Antimalarial Agents

2021 ◽  
Vol 21 (2) ◽  
pp. 452
Author(s):  
Endang Astuti ◽  
Tri Joko Raharjo ◽  
Putra Boang Manalu ◽  
Ilham Satria Putra ◽  
Stephanus Satria Waskitha ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Aldol Condensation ◽  
Antimalarial Activity ◽  
Docking Study ◽  
Docking Studies ◽  
Curcumin Analog ◽  
Molecular Docking Study ◽  
Antimalarial Agents ◽  
Curcumin Analogs ◽  
Ic50 Value

This research involves the synthesis, antimalarial evaluation, and molecular docking of several curcumin analogs. A total of six curcumin analog compounds were synthesized using aldol condensation using hydrochloric acid and sodium hydroxide catalysts. The synthesized compounds were elucidated using FTIR, 1H-NMR, 13C-NMR, and LC-MS/MS. Subsequently, all curcumin analogs were tested as an antimalarial agent against Plasmodium falciparum 3D7 strain, and their mechanism of action was evaluated through a molecular docking study. Six curcumin analogs, i.e. 2,6-bis(2-hydroxybenzylidene)cyclohexanone; 2,6-bis(2-hydroxybenzylidene)cyclopentanone; 1.5-bis(2-hydroxyphenyl)penta-1,4-diene-3-one; 2,6-bis(3-hydroxybenzylidene)cyclo-hexanone; 2,6-bis(3-hydroxybenzylidene)cyclopentanone; and 1,5-bis(3-hydroxy-phenyl)penta-1,4-diene-3-one have been successfully synthesized. In addition, 2,6-bis(2-hydroxybenzylidene) cyclopentanone demonstrated the lowest IC50 value and binding affinity of 0.04 µM and -7.6 kcal/mol, respectively. Based on molecular docking studies, this compound also showed the most potent antimalarial activity targeted at PfATP6.

scholarly journals In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Harvijay Singh
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Viral Infections ◽  
Drug Repurposing ◽  
Docking Study ◽  
Docking Studies ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

Synthesis and Molecular Docking of New Thiophene Derivatives as Lactate Dehydrogenase-A Inhibitors

2019 ◽  
Vol 19 (10) ◽  
pp. 833-841 ◽  
Author(s):  
Abd El-Galil E. Amr ◽  
Mohamed F. El-Shehry ◽  
Alhussein A. Ibrahim ◽  
Hanaa M. Hosni ◽  
Mohamed A. Al-Omar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Lactate Dehydrogenase ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Active Site ◽  
Docking Studies ◽  
Reference Drug ◽  
Molecular Docking Studies ◽  
Thiophene Moiety ◽  
Thiophene Derivatives

Background & Objective: A series of novel derivatives possessing the thiophene moiety were synthesized using ethyl 5'-amino-2,3'-bithiophene-4'-carboxylate as the starting material. Methods: The new synthesized derivatives were screened as lactate dehydrogenase (LDH) inhibitors. LDH plays an important role in glucose metabolism in cancer cells and can affect tumor genesis and metastasis. Results: 3-Substituted p-tolylthieno[2,3-d]pyrimidin-4(3H)-ones 4 were the most potent inhibitors in this study compared to Galloflavin reference drug. Conclusion: Molecular docking studies on the Human Lactate Dehydrogenase active site were carried out on the synthesized compounds and the MolDock scores ranged between -127 to -171.

scholarly journals Aktivitas Antimalaria Daun Erythrina variegata

2018 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Tati Herlina ◽  
Unang Supratman ◽  
Anas Subarnas ◽  
Supriyatna Sutardjo ◽  
Noor Rain Abdullah
Keyword(s):  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Column Chromatography ◽  
Active Compound ◽  
Resistant Strain ◽  
Methanol Extract ◽  
Antimalarial Activity ◽  
Antimalarial Agents ◽  
Erythrina Variegata

The leaves of Erythrina variegata (Leguminosae) used tradisional plant of an antimalarial. In the course of our continuing search for novel an antimalarial compound from Erythrina plants, the methanol extract of the leaves ofE. variegata showed significant antimalarial activity in vitro toward Plasmodium falciparum in vitro using the lactate dehydrogenase (LDH) method. The methanol extract of the leaves of E. variegata showed against bothstrains of parasite with IC50of 6.8 ?g/ml against K1 and > 60 ?g/ml against 3D7, respectively. The methanol extract of the leaves of E. variegata was separated by using bioassay-guide fractionation. The n-buthanol fraction yieldedthe most activity, exhibiting equipotency against both strains of parasite with IC50of 5.1 ?g/ml against K1 and 13.5 ?g/ml against 3D7, respectively. Furthermore, by using the antimalarial activity to follow separation, the n-buthanol fraction was separated by combination of column chromatography to yield an active compound. The active compound showed antimalarial activity against both strains of parasite used with IC50 of 4.3 ?g/ml against K1 and 23.5 ?g/ml against 3D7, respectively. Its inhibition of the resistant strain (K1) was also much better compared to its inhibition of the sensitive strain (3D7), indicated that the leaves of E. variegata to be potential as antimalarial agents, but its lower potency compared to artemisinin and chloroquin.

scholarly journals Pharmacokinetic predictions and docking studies of substituted aryl amine-based triazolopyrimidine designed inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH)

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zakari Ya’u Ibrahim ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Stephen Eyije Abechi
Keyword(s):  
Plasmodium Falciparum ◽  
Docking Studies ◽  
Pharmacokinetic Property ◽  
Skin Permeability ◽  
Dihydroorotate Dehydrogenase ◽  
Data Set ◽  
Molegro Virtual Docker ◽  
Aryl Amine ◽  
Hydrogen Interaction ◽  
Rank Score

Abstract Background The sixteen (16) designed data set of substituted aryl amine-based triazolopyrimidine were docked against Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) employing Molegro Virtual Docker (MVD) software and their pharmacokinetic property determined through SwissADME predictor. Results The docking studies shows compound D16, 5-((6-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)amino)benzo[b]thiophen-4-ol to be the most interactive and stable derivative (re-rank score = − 114.205 kcal/mol) resulting from the hydrophobic as well as hydrogen interactions. The hydrogen interaction produced one hydrogen bond with the active residues LEU359 (H∙∙H∙∙O) at a bond distances of 2.2874 Å. All the designed derivatives were found to pass the Lipinski rule of five tests, supporting the drug-likeliness of the designed compounds. Conclusion The ADME analysis revealed a perfect concurrence with the Lipinski Ro5, where the derivatives were found to possess good pharmacokinetic properties such as molar refractivity (MR), number of rotatable bonds (nRotb), log of skin permeability (log Kp), blood-brain barrier (BBB). These results could a deciding factor for the optimization of novel antimalarial compounds.

scholarly journals Thiazole Based Carbohydrazide Derivatives as α-Amylase Inhibitor and Their Molecular Docking Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Muhammad Taha ◽  
Maryam Irshad ◽  
Syahrul Imran ◽  
Fazal Rahim ◽  
Manikandan Selvaraj ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Docking Study ◽  
Docking Studies ◽  
Antidiabetic Agent ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Structure Activity ◽  
Inhibitory Potential ◽  
Amylase Inhibitors

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as α-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by 1HNMR, 13CNMR, and EI-MS, and evaluated for α-amylase inhibition. Except compound 11 all analogs showed α-amylase inhibitory activity with IC50 values from 1.709 ± 0.12 to 3.049 ± 0.25 μM against the standard acarbose (IC50 = 1.637 ± 0.153 μM). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with IC50 value 1.763 ± 0.03, 1.747 ± 0.20, 1.709 ± 0.12, and 1.948 ± 0.23 μM, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.

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