Design, synthesis and biological evaluation of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors

Wang, Han; Xu, Renyang; Shi, Yipeng; Si, Longlong; Jiao, Pingxuan; Fan, Zibo; Xu, Han; Wu, Xingyu; Zhou, Xiaoshu; Yu, Fei; Zhang, Yongmin; Zhang, Liangren; Zhang, Lihe; Zhou, Demin; Xiao, Sulong

doi:10.1016/j.ejmech.2016.01.005

Cited by 50 publications

(30 citation statements)

References 51 publications

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“…[15, 16] Thus the next generation of antiviral drugs with broad-spectrum antiviral activity against both drug-sensitive and drug-resistant influenza strains is clearly needed. [17, 18]…”

Section: Introductionmentioning

confidence: 99%

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Wang

et al. 2017

European Journal of Medicinal Chemistry

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The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals. In this study we report the design and synthesis of the first class of organosilanes that have potent antiviral activity against a panel of human clinical isolates of influenza A viruses, including viruses that are resistant to amantadine, oseltamivir, or both.

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“…[15, 16] Thus the next generation of antiviral drugs with broad-spectrum antiviral activity against both drug-sensitive and drug-resistant influenza strains is clearly needed. [17, 18]…”

Section: Introductionmentioning

confidence: 99%

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Wang

et al. 2017

European Journal of Medicinal Chemistry

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“…23 Cyclohexanol, 5-methyl-2-(1-methylethenyl) was previously reported with antimicrobial analgesic, anti-inflammatory, sedative, and antifungal properties. 44 Acalypha is the fourth largest genus of Euphorbiaceae family. A. wilkesiana leaves has antimicrobial properties.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Immune Boosting Properties and Combating of Multiple Respiratory Viral Infections by fifteen Euphorbiaceae Plant Extracts

Abd‐Alla¹,

Sweelam²,

El‐Kashak³

et al. 2019

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Objective: Fifteen Euphorbiaceae plant extracts were evaluated for their antiviral and immune boosting properties. Methods: The maximum non-toxic concentration of each extract in specific pathogen-free embryonated chicken eggs was estimated and their antiviral efficacy was determined in terms of reduction in viral titers, measured by the hemagglutination inhibition (HI) assay. The antiviral efficacy was compared with ribavirin. The active extract was further subjected to estimation of total polyphenolic and flavonoid contents. Also, GC/ MS analysis was used to analyze its unsaponifiable and saponifiable matters. Results: The cytotoxic concentration fifty (CC 50 ) of Breynia distacha recorded the value of >200 and >300 for Newcastle disease virus (NDV) and avian influenza virus (AIV) H5N1, respectively. This extract showed antiviral inhibition concentration (IC 50 ) values of ≤ 2 and ≤ 3, respectively and antiviral therapeutic index of 100% compared with ribavirin as standard. The serum of the vaccinated chicks treated with B. distacha has recorded the highest HI titers (7.1 and 8.3 log2) at the day of 28 post vaccination with high protection percentage (100 and 90%) post NDV and AIV H5N1 challenge, respectively. Also, a high HI titer (6.9 log2) was recorded in serum of the vaccinated chicks treated with Aleurites moluccana, Jatropha curcas, Ricinus communis, Putranjiva roxburghii with protection percentage of 95-100% post-NDV challenge. GC/MS analysis allowed identification of 91.10% of the total unsaponifiable matter, (1-heptatriacotanol represented the major component, 24.61%) and 82.51% of the fatty acid methyl esters content (methyl palmitate represented the major component, 26.13 %). Conclusion: This study highlighted the potential of many Euphorbiaceae plants especially B. distacha, to be new candidate of plant-based prototypes that carry antiviral and immunogenic features against respiratory viral infections.has the potential of being more successful in its steps than screening of pure compounds isolated from the products. 8 The spurge family, Euphorbiaceae occupied a special place in the realm of plant families and is scientifically reported for its antiviral, antimicrobial, anticancer, cytotoxic, and antitumor activities. 9 In this respect, the present work aims to search for the use of plants of the Euphorbiaceae family to combat emerging infectious poultry diseases. Fifteen species belong to this family, are widely distributed and easily available throughout various geographical locations in Egypt, 10 were selected and subjected to evaluate their potential anti-viral activities against respiratory tract infection pathogens in specific pathogen-free (SPF) chicken embryos and evaluation of immune boosting properties of these substances in SPF chicks. These plant species are well known to have their traditional claims for cure and/or reduce symptoms of various disorders including infectious diseases of animal and human among folk cultures.

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“…The strategy for the modification of natural compounds of terpene series using click chemistry methodology attracts a considerable attention of experts in organic and medicinal chemistry. For example, rupestonic acid derivatives containing 1,2,3‐triazole fragment were described and studied as AH1N1 influenza virus inhibitors; a large series of oleanolic and betulinic acid conjugates with esters of l ‐ascorbic acid was obtained using the noted methods, these agents showed activity toward A H1N1 influenza virus …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity

Аrtyushin

Moiseeva

Zarubaev

et al. 2019

Chemistry & Biodiversity

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A series of camphecene and quinolizidine alkaloid (−)‐cytisine conjugates has been obtained for the first time using ‘click’ chemistry methodology. The cytotoxicity and virus‐inhibiting activity of compounds were determined against MDCK cells and influenza virus A/Puerto Rico/8/34 (H1N1), correspondingly, in in vitro tests. Based on the results obtained, values of 50 % cytotoxic dose (CC50), 50 % inhibition dose (IC50) and selectivity index (SI) were determined for each compound. It has been shown that the antiviral activity is affected by the length and nature of linkers between cytisine and camphor units. Conjugate 13 ((1R,5S)‐3‐(6‐{4‐[(2‐{(E)‐[(1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐ylidene]amino}ethoxy)methyl]‐1H‐1,2,3‐triazol‐1‐yl}hexyl)‐1,2,3,4,5,6‐hexahydro‐8H‐1,5‐methanopyrido[1,2‐a][1,5]diazocin‐8‐one), which contains cytisine fragment separated from triazole ring by –C6H12– aliphatic linker, showed the highest activity at relatively low toxicity (CC50=168 μmol, IC50=8 μmol, SI=20). Its selectivity index appeared higher than that of reference compound, rimantadine. According to theoretical calculations, the antiviral activity of the lead compound 13 can be explained by its influence on the functioning of neuraminidase.

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Design, synthesis and biological evaluation of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors

Cited by 50 publications

References 51 publications

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

Evaluation of Immune Boosting Properties and Combating of Multiple Respiratory Viral Infections by fifteen Euphorbiaceae Plant Extracts

Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity

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