Induced-Fit Docking Approach Provides Insight into the Binding Mode and Mechanism of Action of HIV-1 Integrase Inhibitors

ChemMedChem ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. 1446-1456 ◽  
Author(s):  
Maria Letizia Barreca ◽  
Nunzio Iraci ◽  
Laura De Luca ◽  
Alba Chimirri
Keyword(s):  
Mechanism Of Action ◽  
Binding Mode ◽  
Integrase Inhibitors ◽  
Induced Fit Docking ◽  
Induced Fit ◽  
Docking Approach ◽  
Insight Into ◽  
Hiv 1

Design, Synthesis and Docking Studies of Thioimidazolyl Diketoacid Derivatives Targeting HIV-1 Integrase

2021 ◽  
Vol 17 ◽  
Author(s):  
Nafiseh Karimi ◽  
Rouhollah Vahabpour Roudsari ◽  
Zahra Hajimahdi ◽  
Afshin Zarghi
Keyword(s):  
Drug Target ◽  
Enzyme Assay ◽  
Binding Mode ◽  
Docking Studies ◽  
Integrase Inhibitors ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Novel Structures ◽  
Anti Hiv ◽  
Hiv 1

Background: Integrase enzyme is a validated drug target to discover novel structures as anti-HIV-1 agents. Objective: Novel series of thioimidazolyl diketo acid derivatives characterizing various substituents at N-1 and 2-thio positions of central ring were developed as HIV-1 integrase inhibitors. Results: The obtained molecules were evaluated in the enzyme assay, displaying promising integrase inhibitory activity with IC50 values ranging from 0.9 to 7.7 M. The synthesized compounds were also tested for antiviral activity and cytotoxicity using HeLa cells infected by the single-cycle replicable HIV-1 NL4-3. Conclusion: The most potent compound was 18i with EC50=19 µM, IC50 0.9 µM and SI= 10.5. Docking studies indicated that the binding mode of the active molecule is well aligned with the known HIV-1 integrase inhibitors.

scholarly journals Multimode, Cooperative Mechanism of Action of Allosteric HIV-1 Integrase Inhibitors

2012 ◽  
Vol 287 (20) ◽  
pp. 16801-16811 ◽  
Author(s):  
Jacques J. Kessl ◽  
Nivedita Jena ◽  
Yasuhiro Koh ◽  
Humeyra Taskent-Sezgin ◽  
Alison Slaughter ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Integrase Inhibitors ◽  
Hiv 1

scholarly journals Argininamide-type neuropeptide Y Y1 receptor antagonists: the nature of Nω-carbamoyl substituents determines Y1R binding mode and affinity

2020 ◽  
Vol 11 (2) ◽  
pp. 274-282
Author(s):  
Jonas Buschmann ◽  
Theresa Seiler ◽  
Günther Bernhardt ◽  
Max Keller ◽  
David Wifling
Keyword(s):  
Neuropeptide Y ◽  
Binding Mode ◽  
Reference Compound ◽  
Induced Fit Docking ◽  
Receptor Antagonists ◽  
Induced Fit ◽  
Y1 Receptor

Replacement of the carbamoyl residue (R) in reference compound 2 by larger residues (e.g.72) strongly affected Y1R affinity. In case of very bulky carbamoyl substituents (e.g.78), an inverted binding mode was suggested by induced-fit docking.

Sequence-Based Design and Discovery of Peptide Inhibitors of HIV-1 Integrase:  Insight into the Binding Mode of the Enzyme

2006 ◽  
Vol 49 (15) ◽  
pp. 4477-4486 ◽  
Author(s):  
Hui-Yuan Li ◽  
Zahrah Zawahir ◽  
Lai-Dong Song ◽  
Ya-Qiu Long ◽  
Nouri Neamati
Keyword(s):  
Binding Mode ◽  
Peptide Inhibitors ◽  
Insight Into ◽  
Hiv 1

Insight into the Inhibitory Mechanism and Binding Mode Between D77 and HIV-1 Integrase by Molecular Modeling Methods

2011 ◽  
Vol 29 (2) ◽  
pp. 311-323 ◽  
Author(s):  
Ping Li ◽  
Jian Jun Tan ◽  
Ming Liu ◽  
Xiao Yi Zhang ◽  
Wei Zu Chen ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Binding Mode ◽  
Inhibitory Mechanism ◽  
Modeling Methods ◽  
Insight Into ◽  
Hiv 1

scholarly journals The mystery of chemistry behind the mechanism of action of anti-HIV drugs: A docking approach at an atomic level

2021 ◽  
Vol 12 (4) ◽  
pp. 432-438
Author(s):  
Mohammad Suhail
Keyword(s):  
Immune System ◽  
Mechanism Of Action ◽  
Computational Study ◽  
Docking Study ◽  
Computational Studies ◽  
Entry Inhibitors ◽  
Docking Approach ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1

The effect of HIV-1 on a human’s immune system cannot be ignored. This is the virus that reduces the power of the immune system to fight against any disease. Of course, many anti-HIV drugs are available, and many computational studies have been done to find out their mechanism of action, but the computational study regarding the chemistry behind the mechanism of action was not done yet. Therefore, the main objective of the study was to clarify the chemistry behind the mechanism of action of commercially available anti-HIV drugs. The drugs taken in the presented study were Entry Inhibitors (EIs) and Non-nucleoside reverse transcriptase inhibitors. First, literature data was evaluated computationally to ensure the reliability of the software used for the presented study. It was found that interaction-based experimental results and computationally evaluated results of the literature data were the same. After that, by following the same procedure, a docking study was done on the drugs taken in the current study. In addition, the residues involved in the interactions of EIs and NNRTIs with their receptors were studied to determine the chemistry that acts behind the action of both. It was found that EIs and NNRTIs work differently. It was also predicted that the derivatization of both drugs could make them more effective and active. Therefore, the presented study will be very helpful in the field of medicinal science.

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