Novel aryl carboximidamide and 3-aryl-1,2,4-oxadiazole analogues of naproxen as dual selective COX-2/15-LOX inhibitors: Design, synthesis and docking studies

Youssif, Bahaa G.M.; Mohamed, Mamdouh F. A.; Al-Sanea, Mohammad M.; Moustafa, Amr H.; Abdelhamid, Antar A.; Gomaa, Hesham A.M.

doi:10.1016/j.bioorg.2019.02.043

Cited by 45 publications

(32 citation statements)

References 37 publications

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“…The inhibitory profile of triclosan and compounds 3 , 8g (models for the higher inhibitory activity) and 8b (model for the deleterious inhibitory activity) were chosen for further investigation by docking into InhA reductase active site (PDB code: 3FNH) to gain insight into the potential binding modes [ 36 , 37 , 38 ]. As a first step, for the validation of docking parameters, the co-crystal ligand (JPJ400) was re-docked at the catalytic site of the protein.…”

Section: Resultsmentioning

confidence: 99%

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In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors

et al. 2020

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Two sets of diphenyl ether derivatives incorporating five-membered 1,3,4-oxadiazoles, and their open-chain aryl hydrazone analogs were synthesized in good yields. Most of the synthesized compounds showed promising in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Three diphenyl ether derivatives, namely hydrazide 3, oxadiazole 4 and naphthylarylidene 8g exhibited pronounced activity with minimum inhibitory concentrations (MICs) of 0.61, 0.86 and 0.99 μg/mL, respectively compared to triclosan (10 μg/mL) and isoniazid (INH) (0.2 μg/mL). Compounds 3, 4, and 8g showed the InhA reductase enzyme inhibition with higher IC50 values (3.28–4.23 µM) in comparison to triclosan (1.10 µM). Correlation between calculated physicochemical parameters and biological activity has been discussed which justifies a strong correlation with respect to the inhibition of InhA reductase enzyme. Molecular modeling and drug-likeness studies showed good agreement with the obtained biological evaluation. The structural and experimental information concerning these three InhA inhibitors will likely contribute to the lead optimization of new antibiotics for M. tuberculosis.

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Section: Resultsmentioning

confidence: 99%

“…Fully automated docking tool using “Dock ligands (CDOCKER)” protocol running on Intel (R) Core (TM) i32370 CPU @ 2.4 GHz, RAM Memory 2 GB under the Windows 7.0 system. The crystal structures of InhA reductase enzyme (PDB code: 3FNH) were downloaded from the protein data bank [ 36 , 37 , 38 ]. See the Supplementary Materials .…”

Section: Methodsmentioning

confidence: 99%

In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors

et al. 2020

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“…Aer the completion of docking, the pose having the lowest energy was chosen to visualize the ligand-protein interaction in Discovery Studio 2017. [27][28][29] 3 Results and discussion…”

Section: Molecular Dockingmentioning

confidence: 99%

Isolation and characterization of novel acetylcholinesterase inhibitors from Ficus benghalensis L. leaves

et al. 2020

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“…Binding Site of Crystallographic Structure of M pro (PDB: 6LU7): Discovery Studio 2.5 software (Accelrys Inc., San Diego, CA, USA) was used for docking analysis. Fully automated docking tool using "Dock ligands (CDOCKER)" protocol running on Intel (R) core (TM) i32370 CPU @ 2.4 GHz 2.4 GHz, RAM Memory 2 GB under the Windows 7.0 system [40][41][42][43] . The X-ray crystallographic structure of M pro complexed with N3 ligand was obtained from the Protein Data Bank through the internet (http://www.…”

Section: Docking Of the Target Molecules To The Activementioning

confidence: 99%

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2020

IJPSR

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The outburst of new coronavirus (COVID-19) infections, firstly appeared in Wuhan in 2019, has massively expanded to the whole world. At the end of March 2020, the rapid spread of the infection happened in about 206 countries around the globe. At the moment, the statistics of WHO on coronavirus pandemic revealed total infected cases of 21,770,000 and more than 77,000 deaths all over the world, with no proven antiviral agent available yet to control COVID-19 infection. The world is currently in desperate need of finding potent therapeutic agents. Histone deacetylases (HDACs) represent one of the most promising viral targets. Importantly, HDACs are critical factors involved in the control of viral replication. The molecular mechanisms associated with underlying the role of HDACs in viral latency, viral reactivation, and carcinogenesis are progressively disclosed. Till now, six HDACIs anticancer drugs have been approved by the FDA. Herein, in the in-silico structurebased drug design approach was utilized to identify novel structural characteristics for the potential repurposed activity of HDACIs as antivirals for COVID-19. In this respect, 12 HDACIs were carefully screened to probe their possible anti-viral activity against SARS-CoV main proteaseM pro (PDB: 6LU7). Most of the screened HDACIs are strongly bind into the active binding site of crystallographic structure of M pro (PDB: 6LU7) with comparable docking energy and hydrogen bond formation. These findings demonstrate that HDACIs, especially Romidepsin and its active form (RedFK), hold promise as COVID-19 protease inhibitors. Moreover, calculations of physicochemical parameters and drug-likeness properties of the screened compounds implied an acceptable ADMET for all tested compounds. INTRODUCTION: In the last few weeks of 2019, an unprecedented global outbreak of novel coronavirus (COVID-19) (2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, detected firstly in Wuhan, China in patients having severe pneumonia 1-5 .

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Novel aryl carboximidamide and 3-aryl-1,2,4-oxadiazole analogues of naproxen as dual selective COX-2/15-LOX inhibitors: Design, synthesis and docking studies

Cited by 45 publications

References 37 publications

In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors

In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors

Isolation and characterization of novel acetylcholinesterase inhibitors from Ficus benghalensis L. leaves

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