A new host-targeted antiviral cyclolignan (SAU-22.107) for Dengue Virus infection in cell cultures. Potential action mechanisms based on cell imaging

Brand, Yaneth M.; Roa-Linares, Vicky C.; Santiago-Dugarte, Carolina; Olmo, Esther del; López-Pérez, Jose Luis; Betancur‐Galvis, Liliana; Gallego-Gómez, Juan Carlos; Feliciano, Arturo San

doi:10.1016/j.virusres.2022.198995

Cited by 4 publications

(7 citation statements)

References 47 publications

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“…Nevertheless, further in vitro experiments are necessary to validate these findings and elucidate the underlying mechanism of action. For example, Brand et al demonstrated that cyclolignan (S.71) reduces viral yield and interferes with DENV genome replication and/or polyprotein translation by altering microtubule distribution and inducing endoplasmic reticulum deterioration 40 . Jung et al revealed that niclosamide inhibits viral RNA replication and also affects the maturation of DENV particles by inducing endosomal neutralization, resulting in the release of non-infectious immature virus particles 41 .…”

Section: Discussionmentioning

confidence: 99%

Dual action effects of ethyl-p-methoxycinnamate against dengue virus infection and inflammation via NF-κB pathway suppression

Tarasuk,

Songprakhon,

Muhamad

et al. 2024

Sci Rep

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Dengue virus (DENV) infection can lead to severe outcomes through a virus-induced cytokine storm, resulting in vascular leakage and inflammation. An effective treatment strategy should target both virus replication and cytokine storm. This study identified Kaempferia galanga L. (KG) extract as exhibiting anti-DENV activity. The major bioactive compound, ethyl-p-methoxycinnamate (EPMC), significantly reduced DENV-2 infection, virion production, and viral protein synthesis in HepG2 and A549 cells, with half-maximal effective concentration (EC50) values of 22.58 µM and 6.17 µM, and impressive selectivity indexes (SIs) of 32.40 and 173.44, respectively. EPMC demonstrated efficacy against all four DENV serotypes, targeting the replication phase of the virus life cycle. Importantly, EPMC reduced DENV-2-induced cytokines (IL-6 and TNF-α) and chemokines (RANTES and IP-10), as confirmed by immunofluorescence and immunoblot analyses, indicating inhibition of NF-κB activation. EPMC's role in preventing excessive inflammatory responses suggests it as a potential candidate for dengue treatment. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness for EPMC were predicted using SwissADME and ProTox II servers, showing good drug-like properties without toxicity. These findings highlight KG extract and EPMC as promising candidates for future anti-dengue therapeutics, offering a dual-action approach by inhibiting virus replication and mitigating inflammatory reactions.

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Section: Discussionmentioning

confidence: 99%

Dual action effects of ethyl-p-methoxycinnamate against dengue virus infection and inflammation via NF-κB pathway suppression

Tarasuk,

Songprakhon,

Muhamad

et al. 2024

Sci Rep

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“…The natural products aglacins A, B, and E were produced by Xu et al via asymmetric photoenolization/Diels-Alder (APEDA) reactions using 2,3,4-trimethoxy-6-methylbenzaldehyde (96) and α-bromolactone (97) (Scheme 7). Smoothly, compound 98 was produced by cycloaddition, and its hydroxyl group was then oxidized to form compound 99 in the presence of 2iodoxybenzoic acid (IBX).…”

Section: Chemical Synthesis Of Aglacinsmentioning

confidence: 99%

“…[95] Moreover, Brand et al suggested that compound 207 (Figure 6) controlled dengue virus in the early stages of infection (within 24 h) and reduced viral production through host-targeted antiviral mechanisms. [96] In recent years, COVID-19 have been rampant and have seriously affected normal human life, for this reason, researchers have been searching for effective target drugs. Rashid et al found that etoposide (200, Figure 5) could be a candidate as a pathogenic protein inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).…”

Section: Antiviral Activities and Their Mechanismsmentioning

confidence: 99%

“…Moreover, Brand et al. suggested that compound 207 (Figure 6) controlled dengue virus in the early stages of infection (within 24 h) and reduced viral production through host‐targeted antiviral mechanisms [96] . In recent years, COVID‐19 have been rampant and have seriously affected normal human life, for this reason, researchers have been searching for effective target drugs.…”

Section: Bioactivities and Mechanisms Of Podophyllotoxin And Its Deri...mentioning

confidence: 99%

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Chemistry and Biology of Podophyllotoxins: An Update

Hao,

2023

Chemistry A European J

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Podophyllotoxin is an aryltetralin lignan lactone derived from different plants of Podophyllum. It consists of five rings with four chiral centers, one trans‐lactone and one aryl tetrahydronaphthalene skeleton with multiple modification sites. Moreover, podophyllotoxin and its derivatives showed lots of bioactivities, including anticancer, anti‐inflammatory, antiviral, and insecticidal properties. The demand for podophyllotoxin and its derivatives is rising as a result of their high efficacy. As a continuation of our previous review (Chem. Eur. J., 2017, 23, 4467–4526), herein, total synthesis, biotransformation, structural modifications, bioactivities, and structure–activity relationships of podophyllotoxin and its derivatives from 2017 to 2022 are summarized. Meanwhile, a piece of update information on the origin of new podophyllotoxin analogues from plants from 2014 to 2022 was compiled. We hope that this review will provide a reference for future high value–added applications of podophyllotoxin and its analogues in the pharmaceutical and agricultural fields.

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“…Its antiviral activity has long been well known [ 205 , 206 ]. In recent literature, examples of antiviral activity of podophyllotoxin derivatives different from the clinical indication against warts can be found [ 207 ]. In this regard, many authors have proposed podophyllotoxin [ 208 ] or etoposide [ 209 ] as useful drugs for the treatment of SARS-CoV-2 infection.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Podophyllotoxin: Recent Advances in the Development of Hybridization Strategies to Enhance Its Antitumoral Profile

Miranda-Vera,

Hernández,

García-García

et al. 2023

Pharmaceutics

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Podophyllotoxin is a naturally occurring cyclolignan isolated from rhizomes of Podophyllum sp. In the clinic, it is used mainly as an antiviral; however, its antitumor activity is even more interesting. While podophyllotoxin possesses severe side effects that limit its development as an anticancer agent, nevertheless, it has become a good lead compound for the synthesis of derivatives with fewer side effects and better selectivity. Several examples, such as etoposide, highlight the potential of this natural product for chemomodulation in the search for new antitumor agents. This review focuses on the recent chemical modifications (2017–mid-2023) of the podophyllotoxin skeleton performed mainly at the C-ring (but also at the lactone D-ring and at the trimethoxyphenyl E-ring) together with their biological properties. Special emphasis is placed on hybrids or conjugates with other natural products (either primary or secondary metabolites) and other molecules (heterocycles, benzoheterocycles, synthetic drugs, and other moieties) that contribute to improved podophyllotoxin bioactivity. In fact, hybridization has been a good strategy to design podophyllotoxin derivatives with enhanced bioactivity. The way in which the two components are joined (directly or through spacers) was also considered for the organization of this review. This comprehensive perspective is presented with the aim of guiding the medicinal chemistry community in the design of new podophyllotoxin-based drugs with improved anticancer properties.

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A new host-targeted antiviral cyclolignan (SAU-22.107) for Dengue Virus infection in cell cultures. Potential action mechanisms based on cell imaging

Cited by 4 publications

References 47 publications

Dual action effects of ethyl-p-methoxycinnamate against dengue virus infection and inflammation via NF-κB pathway suppression

Dual action effects of ethyl-p-methoxycinnamate against dengue virus infection and inflammation via NF-κB pathway suppression

Chemistry and Biology of Podophyllotoxins: An Update

Podophyllotoxin: Recent Advances in the Development of Hybridization Strategies to Enhance Its Antitumoral Profile

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