ISMSC 2007 - Università degli Studi di Pavia

PSB 93
The study of cytotoxicity effect and status of oxidative stress of two novel
synthesized tri-aza macrocyclic diamides as studied in the WI38 cell lines
Massod Mashhadi Akbar Boojar, a Abbas Shockravi, b
a Corresponding and author address: Dr. Massod M. A. Boojar, Department of Biology,
Faculty of Sciences, Tarbiat Moallem University, No: 49, Mofateh Avenue,
P.O.Box:15614. Tehran. Iran.
Tel & Fax: + 9821-88848940 E-mail: aboojar@yahoo.com
b Dr. Abbas Shockravi, Faculty of Chemistry, Tarbiat Moallem University, No: 49,
Mofateh Avenue, P.O.Box: 15614. Tehran. Iran.
Two tri-aza macrocycles as diamide derivatives of macrocyclic compounds, posses a
hydrophilic cavity surrounded by hydrophobic ring, which enable them to diffuse cell membrane
and interfere with different living systems. In this study, we comparatively evaluated cytotoxicity
effects of tri-aza dibenzo sulfoxide (TSD) and dibenzo sulfide (TTS) macrocyclic diamides in a
range of doses (0.25 to 8 mM) and the role of oxidative stress in WI38 cells culture.
We assessed the effects of these substances on ROS level, cellular viability, apoptosis events,
activity of antioxidant enzymes including; superoxide dismutase (SOD), glutathione peroxidase
(GPX), catalase (CAT), and on some macromolecules oxidative damages end-products;
malondialdehyde (MDA), dityrosine and 8-Hydroxy-deoxyguanosine (8-OH-dG) that were
assessed by spectrometry and HPLC methods. Both compounds revealed cytotoxicity effects
on cell culture particularly at doses >1 mM after 24 h incubation. They decreased cellular
viability and significantly promoted ROS generation, increased enzyme activities and enhanced
oxidative damages in which TSD was more effective. Treatment of cells with each compound
alone increased significantly the percent of apoptotic events at 2 and then 4 mM. Co-treatment
with alpha-tocopherol (á-TCP) drastically reduced these events. Cells exposure with mixture of
30 µM alpha–tocopherol and 8 mM of each compound exerted significant decrease on the
levels of ROS, enzyme activities and oxidative damage biomarkers.
As conclusion, our study documented the oxidative radicals forming ability of the studied
compounds and further strengthened the documentation of their cytotoxicity effects through
lipids, proteins and DNA oxidation damages.
Key words: Tri-aza macrocyclic diamides; WI38 cells; Cytotoxicity; Antioxidant enzymes;
Malondialdehyde; Dityrosine; 8-OH-dG; á–tocopherol.
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Shockravi, A.; Bavili, T. S. Journal of Inclusion Phenomena Macrocyclic Chem.
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Pederson, C. J. Sci. 1988, 241, 156.
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PSB 94
Synthesis of photocromic crown containing benzo- and naphtopyranes
Sergey V. Paramonov a , Olga A. Fedorova a , Valerii P. Perevalov a , Vladimir Lokshine b ,
André Samat b
a
Mendeleev University of Chemustry and Technology of Russia, 9, Miusskaya sqr., Moscow,
Russia 125047, e-mail: par.serg@rambler.ru
b
Université de la Méditerranée, Faculté des Sciences de Luminy, UMR 6114, Case 901,
Cedex 9, Marseille, France 13288
One of the interesting approaches to modify the photochromic compounds able to change color
under light irradiation is to introduce an ionophoric moiety (e.g. crown ether) into the molecule.
Due to such a structure the systems involved are able to reveal considerable changes in
spectral and kinetic properties when coordinating with metal ions. These properties are very
important in modern technologies of creating mass storage devices and molecular electronics.
Mn+ hv
Photochromic
transformation
Photochrome
Crownether
Complexation
This work represents syntesis and investigations of novel benzo- and naphthopyranes
containing 18-crown-6 and 15-crown-5-ethers. Due to the molecule structure it is suggested that
complexation and phototransformation processes will influence to each other considerably. Key
reaction of these schemes is the obtaining of chromene structure from crown containing phenol
or naphthol. Two methods were applied: using 1,1-diphenylpropargyl alcohol and -
phenylcinnaroic aldehyde as main reagents.
OH
Ph
Ph
Ph
Ph
OH
CH
O
O Ph
It was showed that all compounds synthesized reveal photochromic properties and they depend
on the crown ether moiety position in the molecule. The results of investigations of the influence
of complexation process on the phototransformation of some substances involved are also
given.
Acknowledgment. All investigations were carried out under support by grant RFFI (No. 05-03-
32268) and exchange program CNRS-RAS.
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