Synthesis of<scp>d</scp>-(+)-camphor-based<i>N</i>-acylhydrazones and their antiviral activity

Kovaleva, Kseniya S.; Zubkov, Fedor I.; Бормотов, Н. И.; Новиков, Роман А.; Dorovatovskii, Pavel V.; Khrustalev, Victor N.; Gatilov, Yuriy V.; Zarubaev, Vladimir V.; Yarovaya, Оlga I.; Шишкина, Л. Н.; Salakhutdinov, N. F.

doi:10.1039/c8md00442k

Cited by 21 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Infectious titer of the virus was determined in MDCK (madin-darby canine kidney) cells (ATCC # CCL-34) in 96-wells plates in alpha-MEM medium (Biolot, St.-Petersburg, Russia). The cytotoxicity assay and virus inhibition assay were performed as previously described [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

et al. 2021

Self Cite

View full text Add to dashboard Cite

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 µM), Ebola pseudotype viruses (IC50 = 0.12 µM), and authentic EBOV (IC50 = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

show abstract

Section: Methodsmentioning

confidence: 99%

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another example presents a series of N -acylhydrazones containing a monoterpene fragment and different aliphatic, aromatic, and heterocyclic pharmacophore scaffolds ( Figure 27 ) [ 96 ]. (+)-Camphor-based N -acylhydrazones exhibit inhibitory activity against vaccinia and influenza viruses.…”

Section: Monoterpene Bicyclic Derivativesmentioning

confidence: 99%

Monoterpenes and Their Derivatives—Recent Development in Biological and Medical Applications

Zielińska-Błajet

Feder‐Kubis

2020

IJMS

220

View full text Add to dashboard Cite

Monoterpenes, comprising hydrocarbons, are the largest class of plant secondary metabolites and are commonly found in essential oils. Monoterpenes and their derivatives are key ingredients in the design and production of new biologically active compounds. This review focuses on selected aliphatic, monocyclic, and bicyclic monoterpenes like geraniol, thymol, myrtenal, pinene, camphor, borneol, and their modified structures. The compounds in question play a pivotal role in biological and medical applications. The review also discusses anti-inflammatory, antimicrobial, anticonvulsant, analgesic, antiviral, anticancer, antituberculosis, and antioxidant biological activities exhibited by monoterpenes and their derivatives. Particular attention is paid to the link between biological activity and the effect of structural modification of monoterpenes and monoterpenoids, as well as the introduction of various functionalized moieties into the molecules in question.

show abstract

“…The chemical compounds library contains 18 agents (1-18) that were screened against OPVs including VARV and four agents (19-22) that were tested against VV. The synthesis of compounds 1 and 2, [17] 3, 5-8, [11] 4, [18] 9-14, [12] and 15-18 [13] was previously described. For the synthesis of derivatives 19, 21, and 22, camphorquinone [19] and camphor hydrazine [13] were prepared according to the procedure reported in the literature from (+)-camphor.…”

Section: Generalmentioning

confidence: 99%

“…This virus is similar to the VARV but can be studied at BSL-2 facilities. Over 300 monoterpenoid derivatives were screened, among which esters 1-4 based on (−)-borneol, amides 5-8 with N-containing heterocycles, [11] the (+)-camphor thiosemicarbazone derivatives 9-14, [12] and (+)-camphor-based N-acylhydrazones 15-18 [13] were found as good inhibitors of the VV (Figure 2). Derivatives 1-18 had IC 50 (the 50% inhibitory concentration) values in the range of 2.5-70 µM against VV and CC 50 (the 50% cytotoxic concentration) values in the range of 120-1430 μM.…”

Section: Introductionmentioning

confidence: 99%

(+)‐Camphor and (−)‐borneol derivatives as potential anti‐orthopoxvirus agents

Соколова

Kovaleva

Yarovaya

et al. 2021

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

Although the World Health Organisation had announced that smallpox was eradicated over 40 years ago, the disease and other related pathogenic poxviruses such as monkeypox remain potential bioterrorist weapons and could also re-emerge as natural infections. We have previously reported (+)-camphor and (−)-borneol derivatives with an antiviral activity against the vaccinia virus. This virus is similar to the variola virus (VARV), the causative agent of smallpox, but can be studied at BSL-2 facilities. In the present study, we evaluated the antiviral activity of the most potent compounds against VARV, cowpox virus, and ectromelia virus (ECTV). Among the compounds tested, 4-bromo-Nʹ-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2ylidene)benzohydrazide 18 is the most effective compound against various orthopoxviruses, including VARV, with an EC 50 value of 13.9 μM and a selectivity index of 206. Also, (+)-camphor thiosemicarbazone 9 was found to be active against VARV and ECTV.

show abstract

Synthesis ofd-(+)-camphor-basedN-acylhydrazones and their antiviral activity

Abstract: CamphorN-acylhydrazones showed promising antiviral activity towards vaccinia and influenza viruses.

Cited by 21 publications

References 42 publications

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Monoterpenes and Their Derivatives—Recent Development in Biological and Medical Applications

(+)‐Camphor and (−)‐borneol derivatives as potential anti‐orthopoxvirus agents

Contact Info

Product

Resources

About