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.

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.

Design, synthesis and biological evaluation of caffeoyl benzanilides as dual inhibitors of HIV integrase and CCR5

MedChemComm ◽  
2016 ◽  
Vol 7 (10) ◽  
pp. 2028-2032 ◽  
Author(s):  
Xuefeng Sun ◽  
Ningning Fan ◽  
Weisi Xu ◽  
Yixing Sun ◽  
Xin Xie ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Hiv Integrase ◽  
Dual Inhibitor ◽  
Design Synthesis ◽  
Dual Inhibitors ◽  
Synthesis And Biological Evaluation ◽  
Hiv 1

Novel series of caffeoyl benzanilides have been synthesized and evaluated as dual inhibitors of HIV-1 CCR5/IN. Compound 9a exhibited the possibility of being a dual inhibitor of HIV-1.

Design, synthesis, and biological evaluation of novel trifluoromethyl indoles as potent HIV-1 NNRTIs with an improved drug resistance profile

2014 ◽  
Vol 12 (21) ◽  
pp. 3446-3458 ◽  
Author(s):  
Hai-Xia Jiang ◽  
Dao-Min Zhuang ◽  
Ying Huang ◽  
Xing-Xin Cao ◽  
Jian-Hua Yao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Resistance Profile ◽  
Drug Resistance Profile ◽  
Synthesis And Biological Evaluation ◽  
Anti Hiv ◽  
Hiv 1

A novel series of trifluoromethyl indoles have been designed, synthesized and evaluated for anti-HIV-1 activities.

Design, Synthesis, and Biological Evaluation of 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole Derivatives as Anti-HIV-1 Agents

2014 ◽  
Vol 85 (6) ◽  
pp. 722-728 ◽  
Author(s):  
Penta Ashok ◽  
Cui-Lin Lu ◽  
Subhash Chander ◽  
Yong-Tang Zheng ◽  
Sankarnarayanan Murugesan
Keyword(s):  
Biological Evaluation ◽  
Indole Derivatives ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Design, synthesis and docking study of acyl thiourea derivatives as possible histone deacetylase inhibitors with a novel zinc binding group

2019 ◽  
Author(s):  
Duraid H Al-Amily ◽  
Mohammed H Mohammed
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Docking Study ◽  
Binding Mode ◽  
Zinc Binding ◽  
Design Synthesis ◽  
Thiourea Derivatives ◽  
Low Cytotoxicity ◽  
New Compounds

Histone deacetylase inhibitors with zinc binding groups often exhibit drawbacks like non-selectivity or toxic effects. Thus, there are continuous efforts to modify the currently available inhibitors or to discover new derivatives to overcome these problems. One approach is to synthesize new compounds with novel zinc binding groups. The present study describes the utilization of acyl thiourea functionality, known to possess the ability to complex with metals, to be a novel zinc binding group incorporated into the designed histone deacetylase inhibitors. N-adipoyl monoanilide thiourea (4) and N-pimeloyl monoanilide thiourea (5) have been synthesized and characterized successfully. They showed good cytotoxicity against cancer cells with low cytotoxicity against normal cells. Their binding mode to the active site of histone deacetylases have been studied by docking study.

Design, Synthesis, and Biological Evaluation of Novel 2-(Pyridin-3-yloxy)acetamide Derivatives as Potential Anti-HIV-1 Agents

2015 ◽  
Vol 87 (2) ◽  
pp. 283-289 ◽  
Author(s):  
Boshi Huang ◽  
Xiao Li ◽  
Peng Zhan ◽  
Erik De Clercq ◽  
Dirk Daelemans ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Betulinic Acid Decorated with Polar Groups and Blue Emitting BODIPY Dye: Synthesis, Cytotoxicity, Cell-Cycle Analysis and Anti-HIV Profiling

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1104
Author(s):  
David Kodr ◽  
Jarmila Stanková ◽  
Michaela Rumlová ◽  
Petr Džubák ◽  
Jiří Řehulka ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Betulinic Acid ◽  
Microscopy Study ◽  
Biological Evaluation ◽  
Cycle Arrest ◽  
Polar Groups ◽  
Mechanism Of Inhibition ◽  
New Compounds ◽  
Anti Hiv ◽  
Hiv 1

Betulinic acid (BA) is a potent triterpene, which has shown promising potential in cancer and HIV-1 treatment. Here, we report a synthesis and biological evaluation of 17 new compounds, including BODIPY labelled analogues derived from BA. The analogues terminated by amino moiety showed increased cytotoxicity (e.g., BA had on CCRF-CEM IC50 > 50 μM, amine 3 IC50 0.21 and amine 14 IC50 0.29). The cell-cycle arrest was evaluated and did not show general features for all the tested compounds. A fluorescence microscopy study of six derivatives revealed that only 4 and 6 were detected in living cells. These compounds were colocalized with the endoplasmic reticulum and mitochondria, indicating possible targets in these organelles. The study of anti-HIV-1 activity showed that 8, 10, 16, 17 and 18 have had IC50i > 10 μM. Only completely processed p24 CA was identified in the viruses formed in the presence of compounds 4 and 12. In the cases of 2, 8, 9, 10, 16, 17 and 18, we identified not fully processed p24 CA and p25 CA-SP1 protein. This observation suggests a similar mechanism of inhibition as described for bevirimat.

Design, Synthesis, and Biological Evaluation of Novel Benzoyl Diarylamine/ether Derivatives as Potential Anti-HIV-1 Agents

2015 ◽  
Vol 86 (3) ◽  
pp. 333-343
Author(s):  
Lingzi Zhang ◽  
Jian Guo ◽  
Xin Liu ◽  
Huiqing Liu ◽  
Erik De Clercq ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation ◽  
Anti Hiv ◽  
Hiv 1
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