Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity

Аrtyushin, О. I.; Шарова, Е. В.; Vinogradova, Natalya M.; Genkina, G. K.; Moiseeva, Aleksandra A.; Klemenkova, Zinaida S.; Orshanskaya, Iana R.; Штро, Анна А.; Kadyrova, Renata A.; Zarubaev, Vladimir V.; Yarovaya, Оlga I.; Salakhutdinov, N. F.; Brel, V. K.

doi:10.1016/j.bmcl.2017.03.051

Cited by 36 publications

(14 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, in this study, we chose to explore modification of methylindole moiety as this region has been demonstrated to be quite tolerant to changes [13]. However, unlike previous studies, we demonstrate the successful implementation of a parallel synthesis strategy using the facile Cu(I)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction ( Fig.1) [29][30][31][32]. This strategy, installs a 1,2,3-triazole unit as a linker in the newly designed compounds, further diversifying the compounds and, most likely, improving solubility ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library

Zalloum

Meuser

et al. 2018

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of HIV-1 replication and is considered an important, clinically unexploited therapeutic target. As such, small drug-like molecules that inhibit this critical HIV-1 protein have become a priority for several groups. Therefore, in this study we explore small molecule targeting of the CA protein, and in particular a very attractive inter-protomer pocket. We report the design, parallel synthesis, and anti-HIV-1 activity evaluation of a series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors synthesized via Cu(I)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. We demonstrate robust inhibitory activity over a range of potencies against the HIV-1 NL reference strain. In particular, compound 13m exhibited the greatest potency and lowest toxicity within this new series with an EC value of 4.33 μM and CC value of >57.74 μM (SI > 13.33). These values are very similar to the lead compound PF-74 (EC = 5.95 μM, CC > 70.50 μM, SI > 11.85) in our assay, despite significant structural difference. Furthermore, we demonstrate via surface plasmon resonance (SPR) binding assays that 13m interacts robustly with recombinant HIV-1 CA and exhibits antiviral activity in both the early and late stages of HIV-1 replication. Overall, the novel parallel synthesis and structure-activity relationships (SARs) identified within this study set the foundation for further rational optimization and discovery of CA-targeting compounds with improved potency.

show abstract

Section: Introductionmentioning

confidence: 99%

Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library

Zalloum

Meuser

et al. 2018

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…The compounds synthesized in this work contain both the monoterpenic fragment and the N-heterocycle. We have previously shown that various derivatives of monoterpenoids, in particular compounds including a 1,7,7-trimethylbicyclo[2.2.1]heptane scaffold and N-heterocyclic fragment, exhibit antiviral properties against the influenza virus [39,40]. In this regard, the obtained derivatives were screened for their inhibitory activity against influenza virus A H1N1.…”

Section: Antiviral Activitymentioning

confidence: 99%

Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity

et al. 2019

Self Cite

View full text Add to dashboard Cite

An effective technique for one-stage synthesis of new polycyclic nitrogen-containing compounds has been developed. The procedure involves refluxing mixtures of camphoric acid with aliphatic or aromatic diamine without catalysts. In cases where the starting amine has a low boiling point (less than 200 °C), phenol is used as a solvent, as it is the most optimal one for obtaining products with good yields. It has been shown that the use of Lewis acids as catalysts reduces the yield of the reaction products. A set of compounds have been synthesized, which can be attributed to synthetic analogues of alkaloids. In vitro screening for activity influenza virus A was carried out for the obtained compounds. The synthesized quinazolinelike agent 14 has inhibitory activity against different strains of influenza viruses.

show abstract

“…Moreover, bispecific antibody conjugated with sortase via click chemistry has broad anti-influenza virus activity (Wagner et al, 2014). In addition, triazole derivatives synthesized by clicking a hydroxyl group or ketogroup onto camphecene showed low cytotoxicity and high antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) (Artyushin et al, 2017).…”

Section: Development Of An Antiviral Agentmentioning

confidence: 99%

Recent trends in click chemistry as a promising technology for virus-related research

et al. 2018

View full text Add to dashboard Cite

Click chemistry involves reactions that were originally introduced and used in organic chemistry to generate substances by joining small units together with heteroatom linkages (C-X-C). Over the last few decades, click chemistry has been widely used in virus-related research. Using click chemistry, the virus particle as well as viral protein and nucleic acids can be labeled. Subsequently, the labeled virions or molecules can be tracked in real time. Here, we reviewed the recent applications of click reactions in virus-related research, including viral tracking, the design of antiviral agents, the diagnosis of viral infection, and virus-based delivery systems. This review provides an overview of the general principles and applications of click chemistry in virus-related research.

show abstract

Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity

Cited by 36 publications

References 33 publications

Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library

Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library

Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity

Recent trends in click chemistry as a promising technology for virus-related research

Contact Info

Product

Resources

About