Læknablaðið : fylgirit - 05.01.2015, Blaðsíða 36

36 LÆKNAblaðið 2011/97
derivatives of the fluorescent labels Rhodamine B and 5-(2-((amino-
oxyacetyl)amino)ethylamino)naphthalene-1-sulfonic acid (EDANS-O-
NH2). Hydroxylamine derivative of heterobifunctional tetra(ethylene
glycol) spacer with protected sulfhydryl group was also synthesized.
The hydroxylamine derivatives were reacted to the reducing end of
chitosan and glucoseamine with aniline catalysed oxime reaction.
The synthesized materials were characterized by NMR and LC-MS
measurement.
Results: The synthesise of all the hydroxylamine derivatives was suc-
cessful. The oxime reaction of glucoseamine with EDANS-O-NH2 and
tetra(ethylene glycol) sulfhydryl spacer was successful and was confir-
med by NMR and LC-MS. The formation of glucoseamine Rhodamine B
product was confirmed by LC-MS. The oxime reaction with EDANS-O-
NH2 and chitosan was achieved. Preliminary results from NMR shows
that chitosan reducing end reacts with tetra(ethylene glycol) sulfhydryl
spacer.
Conclusions: These results demonstrates the proof-of-concept for
selective oxime formation at the reducing end of a chitosan derivatives,
which can be used for tracking chitosan in gene and drug delivery
purposes and gives rise to further modifications with other functional
groups.
E 90 Nýjar N-acyl-dópamín afleiður úr svampdýrinu Myxilla
incrustans sem safnað var á Strýtunum í Eyjafirði
Eydís Einarsdóttir1, Hongbing Liu1, Helga M. Ögmundsdottir2, Elín S. Ólafsdóttir1,
Charlotte H. Gotfredsen3, Sesselja Ómarsdóttir1
1Lyfjafræðideild, 2læknadeild Háskóla Íslands, 3efnafræðideild Tækniháskóla Danmerkur
(DTU)
eydisei@hi.is
Inngangur: Um helmingur allra vestrænna lyfja á rætur sínar að
rekja til náttúrunnar. Flest þessara lyfja eru sýkla- og krabbameinslyf.
Sjávarlífverur eru ákjósanleg uppspretta lífvirkra efna því umhverfi
sjávarlífvera krefst sértækra efna til að komast af í erfiðri lífsbaráttu.
Svampdýr eru frumstæðar lífverur og hefur mörg hundruð mismunandi
efnasamböndum, s.s. alkalóíðum, pólýketíðum, terpenum, fituefnum og
arómatískum efnum, verið lýst. Hafsvæðið í kringum Ísland er einstakt
vistkerfi og þar má m.a. finna heitar uppsprettur eins og strýturnar í
Eyjafirði. Markmið þessa verkefnis var að safna svampdýrasýnum af
Strýtunum, útbúa útdrætti úr þeim og kanna krabbameinshemjandi
áhrif þeirra í rækt. Ennfremur að einangra virku efnin og greina sam-
eindabyggingu þeirra.
Efniviður og aðferðir: 35 svampdýrasýnum var safnað á Strýtunum.
Svampdýrin voru frostþurrkuð og síðan úrhlutuð í CH2Cl2:MeOH (1:1)
í 24 klst. og leysiefni síðan inngufuð frá. Útdrátturinn var síðan þátt-
aður niður með aðlagaðri Kupchan vökvaþáttun í fimm misskautaða
þætti (A, BC, D og E). Krabbameinshemjandi áhrif útdrátta og þátta í
styrknum 33 µg/mL voru könnuð á SkBr-3 krabbameinsfrumur með
MTS aðferð. Einangrun efna var gerð með fastfasasúluskiljun og magn-
bundinni háþrýstivökvaskiljun og sameindabygging ákvörðuð með
massagreiningu og kjarnsegulgreiningu.
Niðurstöður: Átta útdrættir drógu úr lifun krabbameinsfrumanna um
meira en helming. Einn þessara útdrátta var úr svampdýrinu Myxilla
incrustans. Tveir þættir höfðu einnig frumuhemjandi áhrif. Úr þeim
voru einangruð tvo ný efnasambönd sem reyndust vera N-acýl dópamín
afleiður með endastæða glúkúronsýru einingu. Ekki er búið að meta
krabbameinshemjandi áhrif hreinu efnanna.
Ályktanir: Nokkrir útdrættir úr svampdýrum sem safnað var á
Strýtunum höfðu krabbameinshemjandi áhrif í rækt. Þar á meðal úr
svampdýrinu Myxilla incrustans en fáum efnasamböndum hefur verið
lýst úr þessari tegund. Tvær nýjar N-acýl dópamín afleiður með enda-
stæðri sykru voru einangraðar og bygging þeirra ákvörðuð.
E 91 Quaternary N-alkyl and N,N-dialkyl chitosan derivatives as
effective antibacterial agents
Priyanka Sahariah1, Berglind E. Benediktssdóttir1, Martha Á. Hjálmarsdóttir2,
Ólafur E. Sigurjónsson3,4, Kasper K. Sørensen5, Mikkel B. Thygesen5, Már Másson1
1Faculty of Pharmaceutical Sciences, University of Iceland, 2Department of Biomedical Science,
Faculty of Medicine, University of Iceland, 3The REModeL Lab, Blood Bank, Landspítali
University Hospital, 4Institute of Biomedical and Neural Engineering, Reykjavík University,
5Department of Chemistry, Faculty of Science, Centre for Carbohydrate Recognition and
Signalling, University of Copenhagen
prs1@hi.is
Introduction: Chitosan a biopolymer, has been modified to obtain qua-
ternary N-alkyl derivatives for the development of better antibacterial
agents.
Methods and data: Chitosan derivatives were characterized using 1H-
NMR, COSY and IR spectrum. Molecular weight was determined using
GPC. Antibacterial activity was assayed following the CLSI standard
protocols against Staphylococcus aureus (ATCC 29213), Enterococcus
faecalis(ATCC 29212), Escherichia coli (ATCC 25922)and Pseudomonas
aeruginosa (ATCC 27853). Toxicity was determined against human red
blood cells.
Results: A highly efficient method for the regioselective modi-
fication of chitosan biopolymers by means of a simple reductive
amination procedure to yield N,N-dialkyl chitosan derivatives was
developed using four different alkyl chains. The use of 3,6-O-di-tert-
butyldimethylsilylchitosan as a precursor enabled 100% disubstitution
of the amino groups. The corresponding mono N-alkyl derivatives were
also synthesized, and all the alkyl compounds were then quaternized
using an optimized procedure. Antibacterial efficacy against Gram
positive S.aureus, E.faecalis and Gram negative E.coli, P.aeruginosa could
be correlated to the length of the alkyl chain, but the order of activity
was dependent on the bacterial strain. Toxicity against human red
blood cells was found to be proportional to the length of the alkyl chain.
Derivatives having better selectivity than the quaternary ammonium
disinfectants cetylpyridiniumchloride and benzalkoniumchloride as
well as the antimicrobial peptides melittin and LL-37 could be obtained.
Conclusions: The current work has led to the development of compo-
unds having high antibacterial activity and better selectivity. These
being less toxic and more biodegradable are a potential alternative to
antimicrobial peptides and synthetic antimicrobial polymers.
E 92 Stable self-assembled nanoparticles from
sulfobutyl-β-cyclodextrin and chitosan for drug delivery
Zoltán Fülöp1, Attila Balogh2, Phennapha Saokham1, Þorsteinn Loftsson1
1Faculty of Pharmaceutical Sciences, University of Iceland, 2Department of Organic Chemistry
and Technology, Faculty of Chemical Engineering, Budapest University of Technology and
Economics
zof1@hi.is
Introduction: Cyclodextrins are cyclic oligosaccharides with hydrophi-
lic surface and lipophilic cavity. They form inclusion complexes with
lipophilic molecules, increasing the aqueous solubility of various poorly
soluble drugs. Cyclodextrins, their derivatives and their inclusion
X V I I V Í S I N D A R Á Ð S T E F N A H Í
F Y L G I R I T 8 2