Inhibitory Effects of Cembratriene- 4,6-diol Derivatives on the Induction of Epstein-Barr Virus Early Antigen by 12-<i>O</i>-Tetradecanoylphorbol- 13-acetate

Saito, Yutaka; Tsujino, Yasuko; Kaneko, Hajime; Yoshida, Daisuke; Mizusaki, Shigenobu

doi:10.1080/00021369.1987.10868102

Cited by 6 publications

(33 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further studies showed that the cytotoxic mechanism of CBT-diol might be related to its inhibitory effect on protein kinase C (PKC) and phospholipid metabolisms [26]. In contrast to most antineoplastic agents, β-CBT-diol did not show cytotoxicity even at a very high concentration (100 μM) [27]. Nacoulma et al [28] isolated a mixture of cembranoid compounds from the leafy galls of tobacco infested by Rhodococcus fascians , and found that these compounds induced cell enlargement, slowed cell division, and altered the nuclear morphology and the polymerisation and stability of microtubules, and inhibited the proliferation of human glioma cells.…”

Section: Bioactivities Of Tobacco Cembranoid Diterpenesmentioning

confidence: 99%

“…The biocatalysis of tobacco cembranoid diterpenes, which includes hydroxylation, epoxidation and acetylation, mainly involves plant cells, microorganisms and enzymes. The biocatalysis of tobacco cembranoid diterpenes was first reported in 1987 [27]. As far as we know, cembranoid diterpenes are important aroma substances in tobacco [49].…”

Section: Effects Of Biocatalysis On Bioactivities Of Tobacco Cembrmentioning

confidence: 99%

See 1 more Smart Citation

A Review on Bioactivities of Tobacco Cembranoid Diterpenes

Ning

Liu

et al. 2019

Biomolecules

View full text Add to dashboard Cite

Cembranoids are carbocyclic diterpenes comprising four isoprene units and are natural products with a parent skeleton consisting of a 14-membered ring. They have gained wide interest in recent years and are a major hotspot in the research of natural product chemistry. Since 1962, various tobacco cembranoid diterpenes have been identified. This review systematically discusses and summarises the excellent antimicrobial, insecticidal, cytotoxic and neuroprotective activities of tobacco cembranoid diterpenes. These compounds show potential to be developed as botanical fungicides, cytotoxic drugs and drugs for the treatment of human immunodeficiency virus, Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases. However, there are relatively few studies on the structure–activity relationship (SAR) of tobacco cembranoid diterpenes. Therefore, future studies should focus on their structural modification, SAR and biogenic relationships.

show abstract

Section: Bioactivities Of Tobacco Cembranoid Diterpenesmentioning

confidence: 99%

Section: Effects Of Biocatalysis On Bioactivities Of Tobacco Cembrmentioning

confidence: 99%

A Review on Bioactivities of Tobacco Cembranoid Diterpenes

Ning

Liu

et al. 2019

Biomolecules

View full text Add to dashboard Cite

show abstract

“…Saturation of macrocyclic double bonds by catalytic reduction decreased EBA induction, indicating the significance of macrocyclic double bonds for EBA induction inhibitory activity [18]. (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-11S,12S-epoxy-4,6-diol was devoid of activity, suggesting the importance of Δ 11,12 [18]. This study adds insights to establish a preliminary structure-activity relationship for the anti-migratory activity of tobacco (4R)-cembranoids through the use of microbial and semisynthetic optimizations of 2.…”

mentioning

confidence: 96%

“…This may suggest the importance of a hydrogen bond-forming pharmacophore at C-6. Saturation of macrocyclic double bonds by catalytic reduction decreased EBA induction, indicating the significance of macrocyclic double bonds for EBA induction inhibitory activity [18]. (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-11S,12S-epoxy-4,6-diol was devoid of activity, suggesting the importance of Δ 11,12 [18].…”

mentioning

confidence: 99%

“…Only a limited number of structure-activity relationship studies of tobacco cembranoids have been done with the purpose to explore their anticancer activity [15,17]. Acylation of 1 and its C-4 epimer at C-6 using acetic, propionic, butyric, valeric, and benzoic acid anhydrides reduced the Epstein-Barr virus antigen (EBA) formation inhibitory activity by increasing the IC 50 values and cytotoxicity, suggesting the importance of the C-6 hydroxy [15,18]. Cytotoxicity increase was parallel to the increase of the acyl carbon number.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Bioactive Natural, Biocatalytic, and Semisynthetic Tobacco Cembranoids

et al. 2010

View full text Add to dashboard Cite

The two major Nicotiana tabacum tobacco cembranoids, (1 S,2 E,4 R,6 R,7 E,11 E)-2,7,11-cembratriene-4,6-diol (1) and its C-4 epimer, exhibit a wide range of interesting biological activities. Although the tumorigenesis inhibition activity of tobacco cembranoids have been known since the mid 1980's, only a limited number of investigations have targeted their optimization and structure-activity relationship. This study reports the isolation of the new (1 S,2 E,4 S,6 E,8 S,11 E)-2,6,11-cembratriene-8- O-methyl-4,8-diol (3) and the known (1 S,2 E,4 R,6 R,7 E,11 E)-2,7,11-cembratriene-4- O-methyl-4,6-diol (2) from fresh N. tabacum leaves. Cembranoid 2 showed good anti-migratory activity against prostate cancer cell lines, and was therefore subjected to microbial transformation and semisynthetic optimization studies. Biotransformation of 2 using the fungal strains Cunninghamella NRRL 5695 and Mucor ramannianus ATCC 9628 afforded new ( 4 and 5) and known ( 6 and 7) metabolites. Semisynthetic esterification, oxidation, epoxidation, and reaction with Lawesson's reagent afforded the new products 8- 14. Cembranoid 2 and its epoxidation product 9 showed potent anti-migratory activities against the highly metastatic human prostate cancer cell lines PC-3M-CT+ (spheroid disaggregation assay) and PC-3 (wound-healing assay).

show abstract

Chemo-, Regio-, and Stereoselective Oxidation of the Monocyclic Diterpenoid β-Cembrenediol by P450 BM3

et al. 2015

View full text Add to dashboard Cite

Late-stage oxyfunctionalization of terpenoid scaffolds has been recognized as a powerful tool in the synthesis of complex molecules such as natural products to achieve their efficient diversification. Selective C−H oxidation of such hydrocarbon scaffolds remains challenging for chemical catalysts because of their insufficient regio-and stereoselectivity. To achieve this goal, cytochrome P450 monooxygenases are often used as biocatalysts. Here, we demonstrate the successful P450catalyzed chemo-, regio-, and stereoselective oxidation of the tobacco cembranoid β-cembrenediol. This 14-membered macrocycle possesses a broad range of biological activities including antitumor-promoting and neuroprotective effects and carries seven potential sites for allylic hydroxylation as well as three epoxidation sites. On the basis of first-sphere active site mutagenesis, we generated in a few rounds a P450 BM3 minimal library and screened for β-cembrenediol oxidation activity. Several P450 BM3 variants were evolved, enabling the regioselective hydroxylation of the neighboring positions C-9 (100% regioselectivity and a diastereomeric ratio of 89:11 in the case of the F87A/I263L mutant) and C-10 (97% regioselectivity and a diastereomeric ratio of 74:26 in the case of the L75A/V78A/F87G mutant) of β-cembrenediol.

show abstract

Inhibitory Effects of Cembratriene- 4,6-diol Derivatives on the Induction of Epstein-Barr Virus Early Antigen by 12-O-Tetradecanoylphorbol- 13-acetate

Cited by 6 publications

References 5 publications

A Review on Bioactivities of Tobacco Cembranoid Diterpenes

A Review on Bioactivities of Tobacco Cembranoid Diterpenes

Bioactive Natural, Biocatalytic, and Semisynthetic Tobacco Cembranoids

Chemo-, Regio-, and Stereoselective Oxidation of the Monocyclic Diterpenoid β-Cembrenediol by P450 BM3

Contact Info

Product

Resources

About