Synthesis and Preliminary Biologic Evaluation of 5‐Substituted‐2‐(4‐substituted phenyl)‐1,3‐Benzoxazoles as A Novel Class of Influenza Virus A Inhibitors

Li, Zhenyu; Zhan, Peng; Naesens, Lieve; Vanderlinden, Evelien; Liu, Ailin; Du, Guanhua; Clercq, Erik De; Liu, Xinyong

doi:10.1111/j.1747-0285.2012.01344.x

Cited by 7 publications

(2 citation statements)

References 29 publications

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“…Nitro-containing compounds represent a useful and privileged moiety in medicinal chemistry, showing a wide range of biological activities, such as antihypertensive, antineoplastic, antiparasitic, antibiotic, and tranquilizer activities [41]. Nitro-drugs have been studied for their antiviral properties, and some of them are employed as medication [42][43][44]. For this reason, two new analogues, compounds 6 and 7, were synthesized and added to the study to evaluate the role of the position of the nitro group (3 -NO 2 in 13 vs. 4-NO 2 in 6 and 7) and the type of halogen (3 -Cl in 6 vs. 3 -Br in 12) on their activity.…”

Section: Antiviral Activity Of Rsv Derivatives Against Influenza a Vi...mentioning

confidence: 99%

Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents

et al. 2022

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Resveratrol (RSV) is a natural stilbene polyphenolic compound found in several plant species. It is characterized by antioxidant properties, and its role in controlling viral replication has been demonstrated for different viral infections. Despite its promising antiviral properties, RSV biological activity is limited by its low bioavailability and high metabolic rate. In this study, we optimized its structure by synthesizing new RSV derivatives that maintained the phenolic scaffold and contained different substitution patterns and evaluated their potential anti-influenza virus activity. The results showed that viral protein synthesis decreased 24 h post infection; particularly, the nitro-containing compounds strongly reduced viral replication. The molecules did not exert their antioxidant properties during infection; in fact, they were not able to rescue the virus-induced drop in GSH content or improve the antioxidant response mediated by the Nrf2 transcription factor and G6PD enzyme. Similar to what has already been reported for RSV, they interfered with the nuclear-cytoplasmic traffic of viral nucleoprotein, probably inhibiting cellular kinases involved in the regulation of specific steps of the virus life cycle. Overall, the data indicate that more lipophilic RSV derivatives have improved antiviral efficacy compared with RSV and open the way for new cell-targeted antiviral strategies.

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Section: Antiviral Activity Of Rsv Derivatives Against Influenza a Vi...mentioning

confidence: 99%

Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents

et al. 2022

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“…Original drug discovery remains a perennial challenge in the realm of biomedical sciences, and phenotypic screening is a fundamental method for identifying first-in-class small-molecule drugs. , There has been a resurgence over the last several years in the enthusiasm for cell-based phenotypic screening, especially in the field of discovering antiviral drugs, because it allows for the direct observation of a more complex cellular response to specific compounds. − In this study, we used a PR8-PB2-Gluc-based phenotypic screening approach established by us to screen an in-house compound library consisting of 400 chemical entities and natural products with different skeletons. We successfully identified a series of imidazo[1,2- a ]pyrazine derivatives that displayed robust broad-spectrum anti-influenza activities, including against the oseltamivir-resistant A/H1N1/pdm09 strain.…”

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confidence: 99%

Identification of the Imidazo[1,2-a]pyrazine Derivative A4 as a Potential Influenza Virus Nucleoprotein Inhibitor

Li,

Ju,

Xing

et al. 2023

ACS Pharmacol. Transl. Sci.

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Influenza A viruses (IAVs) have gradually developed resistance to FDA-approved drugs, which increases the need to discover novel antivirals with new mechanisms of action. Here, we used a phenotypic screening strategy and discovered that the imidazo[1,2a]pyrazine derivative A4 demonstrates potent and broad-spectrum antiinfluenza activity, especially for the oseltamivir-resistant H1N1/pdm09 strain. Indirect immunofluorescence assays revealed that A4 induces clustering of the viral nucleoprotein (NP) and prevents its nuclear accumulation. Furthermore, upon conducting binding analyses between A4 and the influenza NP using surface plasmon resonance assays and molecular docking simulations, we were able to confirm that A4 binds directly to the viral NP. Additionally, A4 exhibits high human plasma metabolic stability (remaining 120 min > 90%, T 1/2 = 990 min) and moderate inhibitory effects on CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 as well as low acute toxicity in Kunming mice. Overall, this study provides valuable insights and lays the groundwork for future efforts in medicinal chemistry to identify effective drugs against influenza.

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Targeting disease with benzoxazoles: a comprehensive review of recent developments

Abdullahi,

Yeong

2024

Med Chem Res

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Benzoxazole is an attractive scaffold in medicinal chemistry due to its diverse biological applications. From 2016 to 2023, a plethora of benzoxazole derivatives have been synthesized and evaluated for their pharmacological activities but a review on this topic was found lacking. This review thus aims to fill the gap and discusses the pharmacological activities of the synthesized derivatives, emphasizing their interactions with key biological targets implicated in diseases such as cancer, diabetes, pain, inflammation, and cardiovascular disorders. Relevant works were selected mainly from databases such as PubMed and Google Scholar to offer a comprehensive overview of derivatives with promising bioactivities. The limitations pertinent to some derivatives, such as poor in vitro or in vivo activities, were highlighted, while their prospects in drug discovery was discussed.

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Synthesis and Preliminary Biologic Evaluation of 5‐Substituted‐2‐(4‐substituted phenyl)‐1,3‐Benzoxazoles as A Novel Class of Influenza Virus A Inhibitors

Cited by 7 publications

References 29 publications

Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents

Nitrostilbenes: Synthesis and Biological Evaluation as Potential Anti-Influenza Virus Agents

Identification of the Imidazo[1,2-a]pyrazine Derivative A4 as a Potential Influenza Virus Nucleoprotein Inhibitor

Targeting disease with benzoxazoles: a comprehensive review of recent developments

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