Phenolic Diterpenoid Derivatives as Anti-Influenza A Virus Agents

Dang, Zhao; Jung, Katherine; Zhu, Li; Xie, Hua; Lee, Kuo Hsiung̀; Chen, Chin Ho; Huang, Li

doi:10.1021/ml500533x

Cited by 22 publications

(20 citation statements)

References 27 publications

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“…Furthermore, the wide range of biological activities exhibited by similar terpenoids, including those isolated from Salvia species, may make them attractive synthetic targets. [42–47] We anticipate that such compounds could be readily synthesized, using in the described approaches, with minimal modification. Consequently, most of our synthetic efforts are focused on generating the Suzuki coupling precursors i.e., building in substitutions and functionality prior to the key carbon-carbon bond forming step.…”

Section: Resultsmentioning

confidence: 99%

Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors

Binder

Hatfield

Chi

et al. 2018

European Journal of Medicinal Chemistry

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Recently, a series of selective human carboxylesterase inhibitors have been identified based upon the tanshinones, with biologically active molecules containing a 1,2-dione group as part of a naphthoquinone core. Unfortunately, the synthesis of such compounds is complex. Here we describe a novel method for the generation of 1,2-dione containing diterpenoids using a unified approach, by which boronic acids are joined to vinyl bromo-cyclohexene derivatives via Suzuki coupling, followed by electrocyclization and oxidation to the o-phenanthroquinones. This has allowed the construction of a panel of miltirone analogues containing an array of substituents (methyl, isopropyl, fluorine, methoxy) which have been used to develop preliminary SAR with the two human carboxylesterase isoforms. As a consequence, we have synthesized highly potent inhibitors of these enzymes (K < 15 nM), that maintain the core tanshinone scaffold. Hence, we have developed a facile and reproducible method for the synthesis of abietane analogues that have resulted in a panel of miltirone derivatives that will be useful tool compounds to assess carboxylesterase biology.

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Section: Resultsmentioning

confidence: 99%

Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors

Binder

Hatfield

Chi

et al. 2018

European Journal of Medicinal Chemistry

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“…The lathyrane-type diterpenoids from Euphorbia micractina showed the anti-HIV activity [ 27 ]. Dang et al recently reported that the abietane-type tricyclic phenolic diterpenoids, (+)-podcarpic acid and (+)-totarol, inhibited influenza A H1N1 viral infection (A/PR/8/34) [ 28 ]. Therefore, the diterpenoids contained in J. multifida may confer the anti-viral effects such as anti-influenza and anti-HIV activities.…”

Section: Discussionmentioning

confidence: 99%

Anti-influenza virus activity of extracts from the stems of Jatropha multifida Linn. collected in Myanmar

Shoji

Woo

Masuda

et al. 2017

BMC Complement Altern Med

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BackgroundTo contribute to the development of novel anti-influenza drugs, we investigated the anti-influenza activity of crude extracts from 118 medicinal plants collected in Myanmar. We discovered that extract from the stems of Jatropha multifida Linn. showed anti-influenza activity. J. multifida has been used in traditional medicine for the treatment of various diseases, and the stem has been reported to possess antimicrobial, antimalarial, and antitumor activities. However, the anti-influenza activity of this extract has not yet been investigated.MethodsWe prepared water (H2O), ethyl acetate (EtOAc), n-hexane (Hex), and chloroform (CHCl3) extracts from the stems of J. multifida collected in Myanmar, and examined the survival of Madin-Darby canine kidney (MDCK) cells infected with the influenza A (H1N1) virus, and the inhibitory effects of these crude extracts on influenza A viral infection and growth in MDCK cells.ResultsThe H2O extracts from the stems of J. multifida promoted the survival of MDCK cells infected with the influenza A H1N1 virus. The EtOAc and CHCl3 extracts resulted in similar, but weaker, effects. The H2O, EtOAc, and CHCl3 extracts from the stems of J. multifida inhibited influenza A virus H1N1 infection; the H2O extract possessed the strongest inhibitory effect on influenza infection in MDCK cells. The EtOAc, Hex, and CHCl3 extracts all inhibited the growth of influenza A H1N1 virus, and the CHCl3 extract demonstrated the strongest activity in MDCK cells.ConclusionThe H2O or CHCl3 extracts from the stems of J. multifida collected in Myanmar demonstrated the strongest inhibition of influenza A H1N1 viral infection or growth in MDCK cells, respectively. These results indicated that the stems of J. multifida could be regarded as an anti-influenza herbal medicine as well as a potential crude drug source for the development of anti-influenza compounds.

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“…Since the fragments of lactoferrin like lactoferricin have high potency in some biological activities, fragments of the other milk proteins may likewise have considerable antiviral activity and can be chemically synthesized and used instead of the parent milk proteins. A great deal of effort has been directed to the search of natural products with suppressive activity on various viruses (Harnett et al 2005;Tshikalange et al 2008;Klos et al 2009;Ghosh et al 2010;Chen et al 2013;Mulder et al 2013;Shin et al 2013;Alfajaro et al 2014;Wang et al 2014;Xu et al 2014;Dang et al 2015). We have in milk a combination of proteins with activity against a diversity of viruses.…”

Section: Discussionmentioning

confidence: 99%

Antiviral activities of whey proteins

Cheung

Wong

et al. 2015

Appl Microbiol Biotechnol

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Milk contains an array of proteins with useful bioactivities. Many milk proteins encompassing native or chemically modified casein, lactoferrin, alpha-lactalbumin, and beta-lactoglobulin demonstrated antiviral activities. Casein and alpha-lactalbumin gained anti-HIV activity after modification with 3-hydroxyphthalic anhydride. Many milk proteins inhibited HIV reverse transcriptase. Bovine glycolactin, angiogenin-1, lactogenin, casein, alpha-lactalbumin, beta-lactoglobulin, bovine lactoferrampin, and human lactoferrampin inhibited HIV-1 protease and integrase. Several mammalian lactoferrins prevented hepatitis C infection. Lactoferrin, methylated alpha-lactalbumin and methylated beta-lactoglobulin inhibited human cytomegalovirus. Chemically modified alpha-lactalbumin, beta-lactoglobulin and lysozyme, lactoferrin and lactoferricin, methylated alpha-lactalbumin, methylated and ethylated beta-lactoglobulins inhibited HSV. Chemically modified bovine beta-lactoglobulin had antihuman papillomavirus activity. Beta-lactoglobulin, lactoferrin, esterified beta-lactoglobulin, and esterified lactoferrindisplayed anti-avian influenza A (H5N1) activity. Lactoferrin inhibited respiratory syncytial virus, hepatitis B virus, adenovirus, poliovirus, hantavirus, sindbis virus, semliki forest virus, echovirus, and enterovirus. Milk mucin, apolactoferrin, Fe(3+)-lactoferrin, beta-lactoglobulin, human lactadherin, bovine IgG, and bovine kappa-casein demonstrated antihuman rotavirus activity.

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Phenolic Diterpenoid Derivatives as Anti-Influenza A Virus Agents

Cited by 22 publications

References 27 publications

Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors

Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors

Anti-influenza virus activity of extracts from the stems of Jatropha multifida Linn. collected in Myanmar

Antiviral activities of whey proteins

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