4th EucheMs chemistry congress

Poster Session 1
s1006
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - organic chemistry
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ChoLeSteroL-Boron CLuSter ConJuGAteS:
SyntheSiS viA dioxAne rinG oPeninG of the
oxoniuM derivAtive of the Boron CLuSter
And PreLiMinAry PhySiCoCheMiCAL And
BioLoGiCAL evALuAtion
M. BiALeK-PietrAS 1 , A.B. oLeJniCzAK 1 ,
S. tAChiKAwA 2 , h. nAKAMurA 2 , z. J. LeSniKowSKi 1
1 Institute of Medical Biology PAS, Laboratory of Molecular
Virology and Biological Chemistry, Lodz, Poland
2 Gakushuin University, Department of Chemistry, Tokyo, Japan
Due to bioorthogonality, lipophilicity or amphiphilicity, rigid,
spherical or ellipsoidal shape, chemical stability and resistance to
catabolism, carboranes and metallacarboranes are often used in
modification of biologically active compounds. The literature
comprises numerous examples in which boron clusters are applied
as surrogates for heterocycles, annulated carbon rings, or most
popularly for substituted or unsubstituted phenyl rings. [1, 2] Among
many low molecular weight compounds modified with boron
clusters are amino acids, lipids, carbohydrates, porphyrins, nucleic
acid bases and nucleosides, andDNA groove binders; boron cluster
modified biopolymers include peptides and proteins, nucleic acids
(DNA-oligonucleotides) and oligophosphates. Carboranes have
been used also in preparation of analogues of biologically active
steroids such as estradiol, estrogen receptor modulators or
testosterone. [3]
In this communication a general approach to the synthesis
of novel type of cholesterol-boron cluster conjugates bearing
metallacarborane moiety is described. The method is based on the
dioxane ring opening in the oxonium derivative of the boron
cluster.Possibility of incorporation of the selected conjugates into
lipid bilayers and physicochemical and biological characterization
of the obtained metallacarborane-incrusted liposomes was also
approached.
Acknowledgment: Research co-financed by the European
Regional Development Fund under the Operational Programme
Innovative Economy, grant POIG.01.01.02-10-107/09, to MBP,
ABO and ZJL.
references:
1. Z.J. Lesnikowski, in “Boron Science: New Technologies
and Applications”; 2011; H.S. Narayan Ed., CRC Press,
Boca Raton FL, pp. 3–19
2. Z.J. Lesnikowski et al. J. Organomet. Chem.; 1999; 581;
156–169
3. R.N. Grimes; Carboranes, 2011; sec. ed.; Elsevier;
1053–1082
Keywords: carboranes; steroids; liposomes;
4 th EucheMs chemistry congress
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n-oxide derivAtiveS of ChoLeSteroL And
LAnoSteroL
u. BiLdziuKeviCh 1, 2 1, 2
, z. wiMMer
1 Institute of Chemical Technology in Prague, Department of
Chemistry of Natural Compounds, Prague 6, Czech Republic
2 Institute of Experimental Botany AS CR v.v.i., Isotope
Laboratory, Prague 4, Czech Republic
Pathogenic microbes and fungi represent a significant
hazard to multicellular organisms, including humans. In nature,
there are substances capable of selectively inhibit the growth of
microbes and fungi. Some of these substances contain a peroxide
group. We assumed that substances bearing the N-oxide group
also will have the desired properties. Our goal was to prepare
derivatives of phytosterols containing N-oxide group for
subsequent tests of the biological activity.
Lanosterol and cholesterol were selected as representatives
of sterols. For each steroid a series of derivatives was obtained.
We obtained four series of derivatives. Each series consisted of
derivatives containing the N-oxide fragment and derivatives
without theN-oxide fragment. As a basis containing the
N-oxide fragment were selected picolylamine derivatives and
2-(4-aminomethylphenyl)pyridine-N-oxide. They were obtained
in three synthetic stages. Synthesis consisted in protection of the
amino group by obtaining FMOC derivative, oxidation by peracetic
acid for obtaining N-oxide and removing protection group. From
the initial steroids hemiesters of succinic acid were obtained.
Modified amines bearing N-oxide group were coupled with the
sterol hemiesters by amide bond. For comparing biological
activity, we obtained derivatives of phytosterol hemiesters
with picolylamines and 2-(4-aminomethylphenyl)pyridine.
The resulting derivatives were tested for cytotoxicity on the
cells of human T-lymphoblastic leukemia, breast adenocarcinoma,
cervical cancer, and also on normal human fibroblasts.
Acknowledgment: A financial support from specific university
research (MSMT No. 21/2012), project P503/11/0616 (GACR)
and the research program MSM6046137305 (MSMT) is
gratefully acknowledged.
Keywords: steroids; amines; amides; cytotoxicity;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc