Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesis

Nugteren, D.H.; Christ-Hazelhof, E.

doi:10.1016/0090-6980(87)90022-0

Cited by 82 publications

(51 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Falcarindiol also showed antinociceptive activities in the retrograde injection test of bradykinin into a carotid artery of rats. Bioactive crepenynic acid (33) was obtained from crude extracts of Crepis rubra (66)(67)(68)(69). Three compounds, 6, 21, and 34, have also been isolated from carrots and other root crops, and their phytoprotective, cytotoxic, and allergic properties reviewed (70,71).…”

Section: Acetylenic Metabolites From Plant Speciesmentioning

confidence: 99%

Anticancer activity of natural and synthetic acetylenic lipids

Dembitsky¹

2006

Lipids

127

View full text Add to dashboard Cite

This review is a comprehensive survey of acetylenic lipids and their derivatives, obtained from living organisms, that have anticancer activity. Acetylenic metabolites belong to a class of molecules containing triple bond(s). They are found in plants, fungi, microorganisms, and marine invertebrates. Although acetylenes are common as components of terrestrial plants, fungi, and bacteria, it is only within the last 30 years that biologically active polyacetylenes having unusual structural features have been reported from plants, cyanobacteria, algae, invertebrates, and other sources. Naturally occurring aquatic acetylenes are of particular interest since many of them display important biological activities and possess antitumor, antibacterial, antimicrobial, antifouling, antifungal, pesticidal, phototoxic, HIV-inhibitory, and immunosuppressive properties. There is no doubt that they are of great interest, especially for the medicinal and/or pharmaceutical industries. This review presents structures and describes cytotoxic and anticancer activities only for more than 300 acetylenic lipids and their derivatives isolated from living organisms.

show abstract

Section: Acetylenic Metabolites From Plant Speciesmentioning

confidence: 99%

Anticancer activity of natural and synthetic acetylenic lipids

Dembitsky¹

2006

Lipids

127

View full text Add to dashboard Cite

show abstract

“…In tissues such as vesicular gland which have low levels of ⌬ 5 -desaturase activity and thus low levels of AA, DHLA is converted efficiently to 1-series prostanoid products that are found in abundance in semen (25). Other less common fatty acids can also serve as cyclooxygenase substrates including adrenic acid (22:4(n-6)) (28), the Mead acid (5Z,8Z,11Z-eicosatrienoic acid) (29), columbinic acid (5E,9Z,12Z-octadecatrienoic acid) (30,31), and 5,6-oxido-eicosatrienoic acid (32,33). Substrates other than AA typically have somewhat higher K m values than AA but can compete with AA for the cyclooxygenase active site thereby inhibiting formation of 2-series prostanoids.…”

mentioning

confidence: 99%

Mutational and X-ray Crystallographic Analysis of the Interaction of Dihomo-γ-linolenic Acid with Prostaglandin Endoperoxide H Synthases

Thuresson

Malkowski

Lakkides

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Prostaglandin endoperoxide H synthases-1 and -2 (PGHSs) catalyze the committed step in prostaglandin biosynthesis. Both isozymes can oxygenate a variety of related polyunsaturated fatty acids. We report here the x-ray crystal structure of dihomo-␥-linolenic acid (DHLA) in the cyclooxygenase site of PGHS-1 and the effects of active site substitutions on the oxygenation of DHLA, and we compare these results to those obtained previously with arachidonic acid (AA). DHLA is bound within the cyclooxygenase site in the same overall Lshaped conformation as AA. C-1 and C-11 through C-20 are in the same positions for both substrates, but the positions of C-2 through C-10 differ by up to 1.74 Å. In general, substitutions of active site residues caused parallel changes in the oxygenation of both AA and DHLA. Two significant exceptions were Val-349 and Ser-530. A V349A substitution caused an 800-fold decrease in the V max /K m for DHLA but less than a 2-fold change with AA; kinetic evidence indicates that C-13 of DHLA is improperly positioned with respect to Tyr-385 in the V349A mutant thereby preventing efficient hydrogen abstraction. Val-349 contacts C-5 of DHLA and appears to serve as a structural bumper positioning the carboxyl half of DHLA, which, in turn, positions properly the -half of this substrate. A V349A substitution in PGHS-2 has similar, minor effects on the rates of oxygenation of AA and DHLA. Thus, Val-349 is a major determinant of substrate specificity for PGHS-1 but not for PGHS-2. Ser-530 also influences the substrate specificity of PGHS-1; an S530T substitution causes 40-and 750-fold decreases in oxygenation efficiencies for AA and DHLA, respectively.

show abstract

“…Secondly, the extract possesses an inhibitor of the arachidonic acid cascade that blocks these molecules, hindering the suppressive activity of prostaglandins in macrophages. Thus, Nugteren and Christ-Hazelhof (1987) verified that a fatty acid from J. mimosifolia, namely, jacarandic acid, was a good inhibitor of cyclooxygenase with a similar activity to indomethacin, a recognized anti-inflammatory drug, which when used in leishmaniasis polarizes the immune response toward T helper 1 type (Perez-Santos and Talamas-Rohana 2001), a permissive factor for eliminating the infection. Later, Ali and Houghton (1999) isolated three inhibitory active compounds of the lipoxygenase from J. filicifolia.…”

Section: Discussionmentioning

confidence: 51%

Anti-leishmania activity of semi-purified fraction of Jacaranda puberula leaves

et al. 2007

View full text Add to dashboard Cite

The crude methanolic extract from leaves of Jacaranda puberula showed activity against Leishmania (Leishmania) amazonensis. The extract presented active against promastigote forms with an inhibitory concentration 50% (IC(50)) value of 88.0 mug/ml, but only moderated activity against amastigote forms; however in higher concentrations the extract showed cytotoxic effects. The bio-guided chromatographic fractionation the crude methanolic extract against amastigotes yielded a fraction with an IC(50) value of 14.0 mug/ml (without cytotoxic activity) in relation to the crude extract (IC(50) value, 359.0 microg/ml). These data indicate that J. puberula leaves contain active compounds, which should be further investigated for the development of new potential drugs against cutaneous leishmaniasis.

show abstract

Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesis

Cited by 82 publications

References 21 publications

Anticancer activity of natural and synthetic acetylenic lipids

Anticancer activity of natural and synthetic acetylenic lipids

Mutational and X-ray Crystallographic Analysis of the Interaction of Dihomo-γ-linolenic Acid with Prostaglandin Endoperoxide H Synthases

Anti-leishmania activity of semi-purified fraction of Jacaranda puberula leaves

Contact Info

Product

Resources

About