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 Design, Synthesis and Docking Studies of Novel 1, 2, 3-Triazolyl Phenylthiazole Analogs as Potent Anti-HIV-1 NNRT Inhibitors

2017 ◽  
Vol 7 (10) ◽  
Author(s):  
Suresh C Jadhavar ◽  
Sujit G Bhansali ◽  
Shivaji B Patwari ◽  
Sudhakar R Bhusare ◽  
Hanmant M Kasralikar
Keyword(s):  
Docking Studies ◽  
Design Synthesis ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Design, Synthesis and Docking Studies of New 4-hydroxyquinoline-3-carbohydrazide Derivatives as Anti-HIV-1 Agents

Drug Research ◽  
2013 ◽  
Vol 63 (04) ◽  
pp. 192-197 ◽  
Author(s):  
Z. Hajimahdi ◽  
R. Zabihollahi ◽  
M. Aghasadeghi ◽  
A. Zarghi
Keyword(s):  
Docking Studies ◽  
Design Synthesis ◽  
Anti Hiv ◽  
Hiv 1

Novel Benzoxazin-3-one Derivatives: Design, Synthesis, Molecular Modeling, Anti-HIV-1 and Integrase Inhibitory Assay

2020 ◽  
Vol 16 (7) ◽  
pp. 938-946 ◽  
Author(s):  
Mahdieh Safakish ◽  
Zahra Hajimahdi ◽  
Rouhollah Vahabpour ◽  
Rezvan Zabihollahi ◽  
Afshin Zarghi
Keyword(s):  
Molecular Modeling ◽  
Drug Target ◽  
Design Synthesis ◽  
Metal Chelating ◽  
Hydrophobic Site ◽  
Π Stacking Interaction ◽  
Molecular Modeling Studies ◽  
Inhibitory Potential ◽  
Anti Hiv ◽  
Hiv 1

Introduction: Integrase is a validated drug target for anti-HIV-1 therapy. The second generation integrase inhibitors display π-stacking interaction ability with 3’-end nucleotide as a streamlined metal chelating pharmacophore. Method: In this study, we introduced benzoxazin-3-one scaffold for integrase inhibitory potential as bioisostere replacement strategy of 2-benzoxazolinone. Results: Molecular modeling studies revealed that amide functionality alongside oxadiazole heteroatoms and sulfur in the second position of oxadiazole ring could mimic the metal chelating pharmacophore. The halobenzyl ring occupies hydrophobic site created by the cytidylate nucleotide (DC-16). Conclusion: The most potent and selective compound displayed 110 μM IC50 with a selectivity index of more than 2.

Design, synthesis, and docking studies of new 2-benzoxazolinone derivatives as anti-HIV-1 agents

2017 ◽  
Vol 26 (11) ◽  
pp. 2718-2726 ◽  
Author(s):  
Mahdieh Safakish ◽  
Zahra Hajimahdi ◽  
Rezvan Zabihollahi ◽  
Mohammad R. Aghasadeghi ◽  
Rouhoullah Vahabpour ◽  
...  
Keyword(s):  
Docking Studies ◽  
Design Synthesis ◽  
Anti Hiv ◽  
Hiv 1

Design, Synthesis, Docking Studies and Biological Activities Novel 2,3- Diaryl-4-Quinazolinone Derivatives as Anti-HIV-1 Agents

2019 ◽  
Vol 17 (3) ◽  
pp. 214-222 ◽  
Author(s):  
Zahra Hajimahdi ◽  
Rezvan Zabihollahi ◽  
Mohamad Reza Aghasadeghi ◽  
Afshin Zarghi
Keyword(s):  
Biological Activities ◽  
Docking Studies ◽  
One Pot ◽  
Design Synthesis ◽  
Replication Assay ◽  
Novel Structure ◽  
Causes Of Deaths ◽  
Quinazolinone Derivatives ◽  
Anti Hiv ◽  
Hiv 1

Background: Although major efforts have been devoted to the effective treatment of HIV-1 infection, it has remained one of the leading causes of deaths around the world. So, development of anti-HIV-1 agents featuring novel structure is essential. Objective: To synthesize novel quinazolinone derivatives and evaluate their anti-HIV-1 activity. Method: In this study, we designed and synthesized a series of novel 2,3-diaryl-4-quinazolinone derivatives using a one-pot multicomponent reaction. Then, the resulting derivatives were evaluated for anti-HIV-1 activity using Hela cell-based single-cycle replication assay. Results: Most of the compounds showed efficacy against HIV-1 replication and the compound 9c exhibited the highest activity with EC50 value of 37 μM. Docking studies indicated that synthesized compounds can interact with the key residues of the HIV-1 integrase active site. Binding of the most active compound was consistent with the HIV-1 integrase inhibitors. Conclusion: Based on our results, these derivatives represent novel lead compounds for the development of new promising anti-HIV-1 agents.

Piroxicam Analogs: Design, Synthesis, Docking Study and Biological Evaluation as Promising Anti-HIV-1 agents

2021 ◽  
Vol 17 ◽  
Author(s):  
Ali Imani ◽  
Sepehr Soleymani ◽  
Rouhollah Vahabpour ◽  
Zahra Hajimahdi ◽  
Afshin Zarghi
Keyword(s):  
Docking Study ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Hiv Integrase ◽  
Active Molecule ◽  
Design Synthesis ◽  
Molecule Docking ◽  
New Compounds ◽  
Anti Hiv ◽  
Hiv 1

Background: Taking the well-known drug, Piroxicam as a lead compound, we designed and synthesized two series of 1,2-benzothiazines 1,1-dioxide derivatives to assay their ability in inhibition of HIV-1 replication in cell culture. Objective: In this study, we describe the synthesis, docking study and biological evaluation of 1,2-benzothiazines 1,1- dioxide derivatives. Results: Most of the new compounds were active in the cell-based anti-HIV-1 assay with EC50 < 50 M. Among them, compounds 7g was found to be the most active molecule. Docking study using 3OYA pdb code on the most active molecule 7g with EC50 values of 10 M showed a similar binding mode to the HIV integrase inhibitors. Conclusion: Since all the compounds showed no remarkable cytotoxicity (CC50> 500 M), the designed scaffold is promising structure for development of new anti-HIV-1 agents.

scholarly journals A BATTLE AGAINST AIDS: NEW PYRAZOLE KEY TO AN OLDER LOCK-REVERSE TRANSCRIPTASE

2016 ◽  
Vol 8 (11) ◽  
pp. 75 ◽  
Author(s):  
Sony Jacob K. ◽  
Swastika Ganguly
Keyword(s):  
Molecular Docking ◽  
Oral Absorption ◽  
Binding Mode ◽  
Docking Studies ◽  
Mode Analysis ◽  
Protein Preparation ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Protein Preparation Wizard

Objective: The reason for the failure of most of the anti-HIV drugs are their poor pharmacokinetics, the poor risk to benefit ratio and the drug resistance. With the objective of developing newer pyrazole scaffolds for effective treatment of HIV, binding mode analysis of designing ligands with the HIV-1RT protein and prediction of key ADME and toxicity parameters of the compounds was in an area of interest.Methods: In this study, molecular docking studies and ADME-T studies were carried out in designing of some novel pyrazole analogs. The protein (PDB ID: 1RT2) was prepared using the Protein Preparation Wizard (Schrodinger Glide 5.0). ADME parameters calculated by QikProp 3.0v and toxicity of designed analogs checked by using two different online software’s namely Lazar and protox.Results: Most of the designed pyrazole analogs have good oral absorption as well as good binding affinity towards HIV-1 reverse transcriptase.Conclusion: Finally total 5 analogs (SGS-2, 3, 12, 13 and 14) from the 14 designed leads were found to be best on the basis of molecular docking and ADME-T studies.

Design, synthesis and anti-HIV-1 evaluation of a series of 5-hydroxypyridine-4-one derivatives as possible integrase inhibitors

2015 ◽  
Vol 24 (12) ◽  
pp. 4113-4127 ◽  
Author(s):  
Mahboubeh Rostami ◽  
Hajar Sirous ◽  
Rezvan Zabihollahi ◽  
Mohammad R. Aghasadeghi ◽  
Seyed Mehdi Sadat ◽  
...  
Keyword(s):  
Integrase Inhibitors ◽  
Design Synthesis ◽  
Anti Hiv ◽  
Hiv 1

Design, Synthesis and Biological Activity of Aromatic Diketone Derivatives as HIV-1 Integrase Inhibitors

2015 ◽  
Vol 11 (2) ◽  
pp. 180-187 ◽  
Author(s):  
Liming Hu ◽  
Zhipeng Li ◽  
Zhanyang Wang ◽  
Gengxin Liu ◽  
Xianzhuo He ◽  
...  
Keyword(s):  
Biological Activity ◽  
Integrase Inhibitors ◽  
Design Synthesis ◽  
Hiv 1
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