Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4

Campos, Guilherme Rodrigues Fernandes; Bittar, Cíntia; Jardim, Ana Carolina Gomes; Shimizu, Jacqueline Farinha; Batista, Mariana Nogueira; Paganini, Éder Ramos; Assis, Letícia Ribeiro de; Bartlett, C. J.; Harris, Mark; Bolzani, Vanderlan da Silva; Regasini, Luís Octávio; Rahal, Paula

doi:10.1099/jgv.0.000808

Cited by 12 publications

(16 citation statements)

References 50 publications

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“…This indirect data, together with molecular docking results, suggests that the observed replication inhibition was unlikely to be due to the direct inhibition of RNA polymerase activity. Similarly, our results demonstrated that FAM E3 did not intercalate with dsRNA, a mechanism of action described for compounds which inhibit HCV replication, another member of Flaviviridae family 45,46 .…”

Section: Discussionsupporting

confidence: 79%

A diarylamine derived from anthranilic acid inhibits ZIKV replication

Silva

Shimizu

Oliveira

et al. 2019

Sci Rep

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Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3Hel) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3Hel.

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Section: Discussionsupporting

confidence: 79%

A diarylamine derived from anthranilic acid inhibits ZIKV replication

Silva

Shimizu

Oliveira

et al. 2019

Sci Rep

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“…To increase the yield and reduce the reaction time, a few drops of DMSO were added to accelerate the reaction successfully. The 1 H NMR spectra of 1,3-dimethoxy-N-methylacridone (1), 1,5-O,O-dimethylcitrusinine-I (2), 1-O-methylcitpressine-II (3), acronycine (4), 5-methoxyacronycine (5) and 1-O-methylcitracridone-II (6) were measured in CDCl3. Lanthanide-induced shift studies with Eu(dpm)3 were carried out with acridones 1-6.…”

Section: Resultsmentioning

confidence: 99%

“…Acridone alkaloids have become an important topic of medicinal chemistry research in recent years, due to the broadband biological activities on the tricyclic acridine ring system for different design and discovery [1,2]. There are numerous pharmacological publications of the acridone alkaloids and their derivatives that have been reported previously, including anticancer [3,4], antivirus [5][6][7], antibacterial and antifungal [7], anticonvulsant [1], anti-acetylcholinesterase [8], etc. These features are attributed to the semiplanar heterocyclic structure, which interacts with different biomolecular targets proved by the docking studies [9].…”

Section: Introductionmentioning

confidence: 99%

Application of Lanthanide Shift Reagent to the 1H-NMR Assignments of Acridone Alkaloids

et al. 2020

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This study investigates the application of the paramagnetic shift reagent tris(dipivaloylmethanato)-europium(III) in NMR spectral studies of permethoxyacridone alkaloids (1–3) and pyranoacridone alkaloids (4–6). The induced chemical shifts (∆δ) of all protons were observed for the same molecule, and were compared to deduce the positions resulting from the distance nearby the Eu(dpm)3. Assignment of the H-2, H-4 and H-8 of polysubstituted acridones could be distinguished based on the least-squares method of lanthanide-induced shifts plotted against the mole ratios of Eu(dpm)3 to the substrate. The developed method is not only potentially useful for determining the planar structures of polysubstituted compounds, such as acridones, anthraquinones, xanthones, flavonoids, and phenanthrenes, but also applicable for their stereochemistry.

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“…The acridone M14 was synthesized using protocols that were previously described by our group, with minor modifications (Campos et al ). A mixture of phloroglucinol (19 mmol), para ‐toluenesulphonic acid (0·5 mmol) and 13 mmol of 2‐amino‐3,4,5‐hydroxybenzoic acid, in 1‐hexanol (65 ml) was refluxed for 8 h. The heterogeneous mixture was stirred with cold hexane.…”

Section: Methodsmentioning

confidence: 99%

A new acridone with antifungal properties againstCandidaspp. and dermatophytes, and antibiofilm activity againstC. albicans

Oliveira

Silva

et al. 2019

J Appl Microbiol

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Aim:The increase in the number of fungal infections worldwide, coupled with the limitations of current antifungal chemotherapy, demand the development of safe and effective new antifungals. Here, we presented the synthesis of a novel acridone (M14) and its antifungal properties against Candida and dermatophytes species. Methods and Results: A series of 17 acridones was designed, synthesized and tested for its antifungal activity. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Only the acridone M14 showed growth-inhibitory activity against reference strains and clinical isolates of Candida and dermatophytes, with MIC range of 7Á81-31Á25 µg ml À1 . Moreover, M14 exhibited fungicidal activity and prevented biofilm formation by C. albicans as well as reduced the viability of preformed biofilms, even at sub-MICs. The confocal laser scanning microscopy analysis revealed that C. albicans hyphal growth was completely inhibited in the presence of M14. Similarly, there was a severe inhibition on hyphal growth of Trichophyton rubrum. We also found that M14 has relatively low toxicity to human fibroblasts. Conclusions: The new acridone M14 has antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans. In addition, M14 is relatively selective to fungal cells compared to human normal cells. Significance and Impact of the Study: Because of its in vitro antifungal activity, anti-Candida biofilm effect and moderate cytotoxicity towards normal human cell, M14 may serve as a valuable lead compound to develop a new antifungal agent.

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Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4

Cited by 12 publications

References 50 publications

A diarylamine derived from anthranilic acid inhibits ZIKV replication

A diarylamine derived from anthranilic acid inhibits ZIKV replication

Application of Lanthanide Shift Reagent to the 1H-NMR Assignments of Acridone Alkaloids

A new acridone with antifungal properties againstCandidaspp. and dermatophytes, and antibiofilm activity againstC. albicans

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