The bioactivity-guided purification of the culture broth of the shipworm endosymbiont Teredinibacter turnerae strain 991H.S.0a.06 yielded a new fatty acid, turneroic acid (1), and two previously described oxylipins (2–3). Turneroic acid (1) is an 18-carbon fatty acid decorated by a hydroxy group and an epoxide ring. Compounds 1–3 inhibited bacterial biofilm formation in Staphylococcus epidermidis, while only 3 showed antimicrobial activity against planktonic S. epidermidis. Comparison of the bioactivity of 1–3 with structurally related compounds indicated the importance of the epoxide moiety for selective and potent biofilm inhibition.
Bioactivity-guided purification of the culture broth of the shipworm endosymbiont Teredinibacter turnerae 991H.S.0a.06 yielded a new fatty acid, turneroic acid (1), and two previously described oxylipins (2-3). Turneroic acid (1) is an 18-carbon fatty acid decorated by a hydroxy group and an epoxide ring. Compounds 1-3 inhibited bacterial biofilm formation in Staphylococcus epidermidis, while only 3 showed antimicrobial activity against planktonic S. epidermidis. Comparison of the bioactivity of 1-3 with structurally related compounds indicated the importance of the epoxide moiety for selective and potent biofilm inhibition.Abstract Figure
Background
Spider venom is a rich cocktail of neuroactive compounds designed to prey
capture and defense against predators that act on neuronal membrane
proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic
transmission through acetylcholine (ACh) hydrolysis - an excitatory
neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid
precursor proteins (APP), which are, in turn, relevant in the structural
integrity of neurons. The present study provides preliminary evidence on the
therapeutic potential of
Phlogiellus bundokalbo
venom
against neurodegenerative diseases.
Methods
Spider venom was extracted by electrostimulation and fractionated by
reverse-phase high-performance liquid chromatography (RP-HPLC) and
characterized by matrix-assisted laser desorption ionization-time flight
mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was
observed by a neurobehavioral response from
Terebrio
molitor
larvae
in vivo
and fractions were
screened for their inhibitory activities against AChE and BACE
in
vitro
.
Results
The whole venom from
P. bundokalbo
demonstrated
neuroactivity by inducing excitatory movements from
T.
molitor
for 15 min. Sixteen fractions collected produced
diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of
sixteen fractions demonstrated AChE inhibitory activities with 14.34% (±
2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (±
3.90e-5) inhibition (p > 0.05), while none of the fractions were observed
to exhibit BACE inhibition. Furthermore, three potent fractions against
AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions
compared to donepezil as the positive control.
Conclusion
The venom of
P. bundokalbo
contains compounds that
demonstrate neuroactivity and anti-AChE activities
in
vitro
, which could comprise possible therapeutic leads for the
development of cholinergic compounds against neurological diseases.
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