Combined strategies in structure-based virtual screening

2020 ◽  
Vol 22 (6) ◽  
pp. 3149-3159 ◽  
Author(s):  
Zhe Wang ◽  
Huiyong Sun ◽  
Chao Shen ◽  
Xueping Hu ◽  
Junbo Gao ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Drug Design ◽  
Lead Compounds

The identification and optimization of lead compounds are inalienable components in drug design and discovery pipelines.

Natural Products of Dietary Origin as Lead Compounds in Virtual Screening and Drug Design

2012 ◽  
Vol 13 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Werner J. Geldenhuys ◽  
Anupam Bishayee ◽  
Altaf S. Darvesh ◽  
Richard T. Carroll
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
Drug Design ◽  
Lead Compounds ◽  
Dietary Origin

scholarly journals Design of Novel Bioisosteres of β-Diketo Acid Inhibitors of HIV-1 Integrase

2005 ◽  
Vol 16 (1) ◽  
pp. 41-61 ◽  
Author(s):  
Mario Sechi ◽  
Luciano Sannia ◽  
Fabrizio Carta ◽  
Michele Palomba ◽  
Roberto Dallocchio ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Drug Design ◽  
Carboxylic Acids ◽  
Active Site ◽  
Docking Studies ◽  
Design Strategies ◽  
Structure Based Drug Design ◽  
Computational Docking ◽  
Lead Compounds ◽  
Hiv 1

HIV-1 integrase (IN) is an attractive and validated target for the development of novel therapeutics against AIDS. Significant efforts have been devoted to the identification of IN inhibitors using various methods. In this context, through virtual screening of the NCI database and structure-based drug design strategies, we identified several pharmacophoric fragments and incorporated them on various aromatic or heteroaromatic rings. In addition, we designed and synthesized a series of 5-aryl(heteroaryl)-isoxazole-3-carboxylic acids as biological isosteric analogues of β-diketo acid containing inhibitors of HIV-1 IN and their derivatives. Further computational docking studies were performed to investigate the mode of interactions of the most active ligands with the IN active site. Results suggested that some of the tested compounds could be considered as lead compounds and suitable for further optimization.

scholarly journals Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4424
Author(s):  
Uzma Arshad ◽  
Sibtain Ahmed ◽  
Nusrat Shafiq ◽  
Zaheer Ahmad ◽  
Aqsa Hassan ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Catalytic Amount ◽  
Pyrimidine Derivatives ◽  
Qsar Studies ◽  
Lead Compounds ◽  
Biological Potential ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Vitro Analysis

Objective: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. Methodology: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. Results: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

scholarly journals Structure-based virtual screening for new lead compounds targeted Plasmodium α-tubulin

2021 ◽  
Vol 28 ◽  
pp. 135-139
Author(s):  
O. V. Rayevsky ◽  
O. M. Demchyk ◽  
P. A. Karpov ◽  
S. P. Ozheredov ◽  
S. I. Spivak ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Protein Interaction ◽  
Specific Binding ◽  
Pharmacophore Model ◽  
Computational Prediction ◽  
Mitotic Apparatus ◽  
Ligand Interaction ◽  
Lead Compounds ◽  
Key Functional Groups ◽  
Potential Inhibitors

Aim. Search for new dinitroaniline and phosphorothioamide compounds, capable of selective binding with Plasmodium α-tubulin, affecting its mitotic apparatus. Methods. Structural biology methods of computational prediction of protein-ligand interaction: molecular docking, molecular dynamics and pharmacophore analysis. Selection of compounds based on pharmacophore characteristics and virtual screening results. Results. The protocol and required structural conditions for target (α-tubulin of P. falciparum) preparation and correct modeling of the ligand-protein interaction (docking and virtual screening) were developed. The generalized pharmacophore model of ligand-protein interaction and key functional groups of ligands responsible for specific binding were identified. Conclusions. Based on results of virtual screening, 22 commercial compounds were selected. Identified compounds proposed as potential inhibitors of Plasmodium mitotic machinery and the base of new antimalarial drugs. Keywords: malaria, Plasmodium, intermolecular interaction, dinitroaniline derived, phosphorothioamidate derived.

scholarly journals In SilicoInvestigation of Potential Pyruvate Kinase M2 Regulators from Traditional Chinese Medicine against Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Kuen-Bao Chen ◽  
Hsin-Yi Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Virtual Screening ◽  
Drug Development ◽  
Pyruvate Kinase ◽  
Md Simulation ◽  
Docking Simulation ◽  
Target Protein ◽  
Binding Affinities ◽  
Pyruvate Kinase M2 ◽  
Lead Compounds ◽  
The Stability

A recent research in cancer research demonstrates that tumor-specific pyruvate kinase M2 (PKM2) plays an important role in chromosome segregation and mitosis progression of tumor cells. To improve the drug development of TCM compounds, we aim to identify potent TCM compounds as lead compounds of PKM2 regulators. PONDR-Fit protocol was utilized to predict the disordered disposition in the binding domain of PKM2 protein before virtual screening as the disordered structure in the protein may cause the side effect and downregulation of the possibility of ligand to bind with target protein. MD simulation was performed to validate the stability of interactions between PKM2 proteins and each ligand after virtual screening. The top TCM compounds, saussureamine C and precatorine, extracted fromLycium chinenseMill. andAbrus precatoriusL., respectively, have higher binding affinities with target protein in docking simulation than control. They have stable H-bonds with residues A:Lys311 and some other residues in both chains of PKM2 protein. Hence, we propose the TCM compounds, saussureamine C and precatorine, as potential candidates as lead compounds for further study in drug development process with the PKM2 protein against cancer.

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