APITOXINA & ANTINFLAMATORIO
| 1: J Org Chem. 2004 Aug 20;69(17):5712-9. |
Total syntheses
of (+)- and (-)-cacospongionolide B, cacospongionolide
e, and related analogues. Preliminary study of structural features required
for phospholipase a2 inhibition.
Cheung
AK, Murelli
R, Snapper
ML.
Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon
Street, Chestnut Hill, Massachusetts 02467, USA.
The total syntheses of the antiinflammatory marine sponge metabolites (+)-cacospongionolide
B and E are described. The pivotal steps in the synthetic route include a
three-step sequence that couples the two main regions of the natural product,
as well as generates the side chain dihydropyran ring. The activity of the
synthetic analogues against bee venom phospholipase A2 suggests that the cacospongionolides
have enantiospecific interactions with the enzyme that may be independent
of the gamma-hydroxybutenolide moiety. Copyright 2004 American Chemical Society
PMID: 15307744 [PubMed - indexed
for MEDLINE]
| 2: J Am Chem Soc. 2002 Oct 2;124(39):11584-5. |
Total syntheses
of (+)- and (-)-cacospongionolide B: new insight
into structural requirements for phospholipase A(2) inhibition.
Cheung
AK, Snapper
ML.
Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon
Street, Chestnut Hill, MA 02467, USA.
The first total synthesis of the antiinflammatory marine sponge metabolite
(+)-cacospongionolide B has been accomplished in 12 linear steps. The pivotal
transformations include a three-step sequence coupling the two main regions
of the natural product as well as generating the side chain dihydropyran ring.
The activity of the synthetic analogues against bee venom phospholipase A(2)
suggests that cacospongionolide B has an enantiospecific interaction with
the enzyme that is independent of the gamma-hydroxybutenolide moiety.
PMID: 12296709 [PubMed
- indexed for MEDLINE]
| 3: J Protein Chem. 1992 Jun;11(3):275-80. |
Mast cell degranulating (MCD) peptide analogs with reduced ring
structure.
Buku
A, Reibman
J, Pistelli
A, Blandina
P, Gazis
D.
Department
of Physiology and Biophysics,
Mast cell degranulating (MCD) peptide, a component of bee venom, is a 22 amino
acid peptide with two disulfide bridges. In this first structure-activity
study of MCD peptide, three analogs were synthesized and tested: two analogs
shortened by omitting sequences 6-10 and 8-13, respectively, and one analog
lacking the disulfide bridge between cysteine residues 5 and 19. These analogs
were synthesized by solid-phase methods and were compared to MCD peptide in
two assays for inflammation: histamine release from mast cells and superoxide
anion release from neutrophils. All three analogs produced histamine release,
although with only about one fifth of the activity of MCD peptide. Superoxide
anion-releasing activity, however, did not parallel histamine release. MCD
peptide did not release superoxide anion, while the 6-10 and 8-13 deletion
analogs were strong and weak stimulants, respectively, of this anion. CD spectra
showed that the secondary structures of the three analogs were very similar
to that of MCD peptide, so that a change in secondary structure cannot completely
explain the changes in releasing activities. Charge differences between the
two deletion analogs and MCD peptide may explain some of the differences in
activity. This is the first demonstration that the various activities of MCD
peptide can be separated, and provides a lead through which the purported
antiinflammatory activity of MCD peptide may possibly be explored in the future.
PMID: 1382440 [PubMed
- indexed for MEDLINE]
| 4: Inflammation. 1986 Jun;10(2):175-82. |
Bee venom melittin
blocks neutrophil O2- production.
Somerfield SD, Stach
JL, Mraz C, Gervais
F, Skamene E.
Bee venom (BV) is used in folk medicine to treat arthritis. It has antiinflammatory
effects in animal models of rheumatic disease. We have studied the effects
of BV on human neutrophil production of superoxide (O2-) and hydrogen peroxide,
finding potent, nontoxic, dose-dependent production inhibition. Melittin,
the major fraction of BV (50-70%) shows high-affinity calmodulin binding (Kd
3 nM). Drugs which bind calmodulin, such as trifluoperazine, inhibit O2- production
by human neutrophils. For these reasons we have investigated the effect of
melittin and other BV peptides on O2- production by human peripheral blood
leukocytes. We show that melittin inhibited O2- production both pre- and poststimulation
in contrast to other BV fractions which were without effect. Oxygen radicals
and their derivatives from inflammatory cells are implicated in the tissue
damage occurring during inflammation. The inhibition is due to a direct effect
on cells, and not indicator medium, dismutation, toxic or scavenging effects.
We propose that melittin may serve as a prototype small (mol wt 1280), cationic,
amphipathic, calmodulin-binding, membrane-active, superoxide-production-inhibiting
peptide, providing a model for peptides which could have a role in in vivo
regulation of radical production.
PMID: 3011670 [PubMed
- indexed for MEDLINE]
| 5: Acta Physiol Pharmacol Bulg. 1985;11(2):50-5. |
Further investigation on the antiinflammatory properties of adolapin--bee
venom polypeptide.
Koburova KL, Michailova
SG, Shkenderov SV.
Adolapin is a basic polypeptide (M. W. 11500) isolated from bee venom. It
showed marked antiinflammatory and analgetic properties and inhibited cyclooxygenase.
It was found that adolapin inhibited also the activity of bee venom phospholipase
A2 (7 nmole/ml producing about 80% inhibition of 2.5 nmole/ml phospholipase).
In addition it inhibited the lipoxygenase from human platelets (4.5 nmole/ml
inhibited about 80% of the activity of 0.8 mg protein/ml). Adolapin (20 micrograms/kg)
caused an elevation of c-GMP level in rat spleen and brain as well as a decrease
of c-AMP in rat spleen. Adolapin was tested by the "tail flick"
method which allowed the demonstration of its analgetic action. The partial
inhibition of the analgetic effect of adolapin induced by naloxon, proved
the participation of a central mechanism of action. Similar to other nonsteroid
analgetics, adolapin displayed antipyretic effect (40 micrograms/kg caused
an inhibition of the mean temperature rise about 62%.
PMID: 2996298 [PubMed
- indexed for MEDLINE]
| 6: Inflammation. 1984 Dec;8(4):385-91. |
Bee venom inhibits
superoxide production by human neutrophils.
Somerfield SD, Stach
JL, Mraz C, Gervais
F, Skamene E.
Investigation of the antiinflammatory properties of bee venom demonstrates
that it inhibits production of superoxide anion by human neutrophils in a
potent, selective, nontoxic, dose-dependent fashion, both pre- and poststimulation
by particulate and soluble activators of the neutrophil oxidative metabolism
burst. The effect is not due to receptor competition, superoxide dismutase,
and/or catalase activity, scavenging, or indicator media effects. These findings
may explain the antiinflammatory effects of whole bee venom in experimental
systems, its widespread use in folk medicine, and lead to the development
of potent, new antiinflammatory substances for therapeutic use in man.
PMID: 6097547 [PubMed
- indexed for MEDLINE]