3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors

Osman, Hasnah; Idris, Nor Hashima; Kamarulzaman, Ezatul Ezleen; Wahab, Habibah A.; Hassan, Mohd. Zaheen

doi:10.1016/j.apsb.2017.04.009

Cited by 21 publications

(9 citation statements)

References 21 publications

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“…Surprisingly, panduratin A did not exhibit remarkable activity against NS2B/NS3 enzyme, as an IC 50 value of more than 100 μM was expected based on the AlphaScreen ® assay. In fact, protease assay produced an IC 50 value of 211.5 μM when higher concentration range of the compound was tested, a value higher than previously reported [57].…”

Section: Discussioncontrasting

confidence: 55%

“…Other group of compounds studied for their anti-dengue activities include novel thiadiazoloacrylamide analogues with one of these showing moderate activity with IC 50 values at 2.2 μM based on NS2B/NS3 protease assay [56]. Meanwhile, two nitro derivatives of 3,5-bis(arylidene)-4-piperidones were shown to inhibit NS2B/NS3 protease with IC 50 values of 15.22 and 16.23 μM [57]. However, most of these antiviral compounds have only manifested moderate to weak anti-dengue activities.…”

Section: Discussionmentioning

confidence: 99%

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Development of a NS2B/NS3 protease inhibition assay using AlphaScreen® beads for screening of anti-dengue activities

Abduraman

Hariono

Yusof

et al. 2018

Heliyon

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BackgroundDengue infection is an endemic infectious disease and it can lead to dengue fever, dengue hemorrhagic fever, and/or dengue shock syndromes. Dengue NS2B/NS3 protease complex is essential for viral replication and is a primary target for anti-dengue drug development. In this study, a NS2B/NS3 protease inhibition assay was developed using AlphaScreen® beads and was used to screen compounds for their protease inhibition activities.MethodsThe assay system utilized a known NS2B/NS3 peptide substrate, a recombinant of NS2B/NS3 protease with proprietary StrepTactin® donor and nickel chelate acceptor beads in 384-well format.ResultsThe optimized assay to screen for NS2B/NS3 protease inhibitors was demonstrated to be potentially useful with reasonable zʹ factor, coefficient variance and signal to background ratio. However, screening of synthesized thioguanine derivatives using the optimized AlphaScreen® assay revealed weak NS2B/NS3 inhibition activities.ConclusionThe AlphaScreen® assay to screen for NS2B/NS3 protease inhibitors is potentially applicable for high throughput screening.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Development of a NS2B/NS3 protease inhibition assay using AlphaScreen® beads for screening of anti-dengue activities

Abduraman

Hariono

Yusof

et al. 2018

Heliyon

Self Cite

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“…Compound 53 was predicted to formed six hydrogen bonds with His51, Pro132, Ser135, Gly153, Arg54, and Trp50 residues. 96…”

Section: 1 Piperidinyl and Piperidone Derivativesmentioning

confidence: 99%

A short survey of dengue protease inhibitor development in the past 6 years (2015–2020) with an emphasis on similarities between DENV and SARS-CoV-2 proteases

Murtuja

Shilkar

Sarkar

et al. 2021

Bioorganic & Medicinal Chemistry

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Dengue remains a disease of significant concern, responsible for nearly half of all arthropod-borne disease cases across the globe. Due to the lack of potent and targeted therapeutics, palliative treatment and the adoption of preventive measures remain the only available options. Compounding the problem further, the failure of the only dengue vaccine, Dengvaxia®, also delivered a significant blow to any hopes for the treatment of dengue fever. However, the success of Human Immuno-deficiency Virus (HIV) and Hepatitis C Virus (HCV) protease inhibitors in the past have continued to encourage researchers to investigate other viral protease targets. Dengue virus (DENV) NS2B-NS3 protease is an attractive target partly due to its role in polyprotein processing and also for being the most conserved domain in the viral genome. During the early days of the COVID-19 pandemic, a few cases of Dengue-COVID 19 co-infection were reported. In this review, we compared the substrate-peptide residue preferences and the residues lining the sub-pockets of the proteases of these two viruses and analyzed the significance of this similarity. Also, we attempted to abridge the developments in anti-dengue drug discovery in the last six years (2015–2020), focusing on critical discoveries that influenced the research.

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“…DEN1, DEN2, DEN3 and DEN4, are very closely related serotypes; thus their cross-reactive antibodies aggravate the risk of severe dengue shock in people experiencing repeated dengue virus (DENV) infections. [23,24] Currently, no effective treatments are available for dengue. Most investigational new anti-dengue agents directly target the viral structural proteins (capsid [C], prM and E) or nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) by cellular proteases and viral serine protease, composed of NS2B and NS3.…”

Section: Anti-dengue Agentsmentioning

confidence: 99%

Benzothiazoles as potential antiviral agents

Asiri

Alsayari

Muhsinah

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives The recent viral pandemic poses a unique challenge for healthcare providers. Despite the remarkable progress, the number of novel antiviral agents in the pipeline is woefully inadequate against the evolving virulence and drug resistance of current viruses. This highlights the urgent need for new and improved vaccines, diagnostics and therapeutic agents to obviate the viral pandemic. Key findings Benzothiazole plays a pivotal role in the design and development of antiviral drugs. This is evident from the fact that it comprises many clinically useful agents. The current review is aimed to provide an insight into the recent development of benzothiazole-based antiviral agents, with a special focus on their structure-activity relationships and lead optimisation. One hundred and five articles were initially identified, and from these studies, 64 potential novel lead molecules and main findings were highlighted in this review. Summary We hope this review will provide a logical perspective on the importance of improving the future designs of novel broad-spectrum benzothiazolebased antiviral agents to be used against emerging viral diseases. Benzothiazoles as antiviral agents Yahya I. Asiri et al.

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3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors

Cited by 21 publications

References 21 publications

Development of a NS2B/NS3 protease inhibition assay using AlphaScreen® beads for screening of anti-dengue activities

Development of a NS2B/NS3 protease inhibition assay using AlphaScreen® beads for screening of anti-dengue activities

A short survey of dengue protease inhibitor development in the past 6 years (2015–2020) with an emphasis on similarities between DENV and SARS-CoV-2 proteases

Benzothiazoles as potential antiviral agents

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