Cancer Research Institute, Slovak Academy of Sciences

L17
SYNTHESIS AND ANTITUMOR ACTIVITY OF COMPOUNDS BASED
ON 9-ISOTHIOCYANATOACRIDINE
Imrich, J., Balentová, E., Géci, I., Vilková, M., Tomaščiková, J., Ungvarský, J., Drajna,
L.,and Kristian, P.
P. J. Šafárik University, Faculty of Science, Institute of Chemistry,
Moyzesova 11, 04167 Košice, Slovak Republic
An original synthon, 9-isothiocyanatoacridine, prepared by Kristian in 1961, has
been broadly utilized in our laboratory for numerous syntheses of various classes of new
acyclic and heterocyclic compounds possessing moderate antitumor activity in past fifteen
years.
The sets of newly prepared compounds comprised acridinyl and 9,10-dihydroacridinyl
thioureas, ureas, thiocarbamates, dithiocarbamates, thiosemicarbazides and
hydrazones as intermediates and spirodihydroacridines and acridinyl thiazolidines,
imidazolines, thiazines, isooxazolines, and oxadiazoles as final heterocyclic structures.
This synthetic variability inspired our search for new synthetic analogues, where
structures based on 3,6-disothiocyanatoacridine, 9-isothiocyanato-1,2,3,4-tetrahydro-
acridine and sugar isothiocyanates proved to be promising synthons, fluorogens, and/or
biomarkers.
Due to the presence of a planar acridine skeleton, intercalating properties have
been studied by spectral methods and antitumor activity has been proved for many target
compounds in collaborations with several laboratories in Slovakia and abroad.
L18
COMPUTER-ASSISTED COMBINATORIAL DRUG DESIGN
Frecer, V.
Cancer Research Institute, Slovak Academy of Sciences, SK-83391 Bratislava, Slovakia
vladimir.frecer@savba.sk
The last decades has witnessed a technological revolution in molecular design,
material science and nanotechnology. Combinatorial chemistry, parallel synthesis and
high-throughput screening as well as computational design techniques have been embraced
by numerous industry sectors as the means to accelerate the discovery of new molecules
and materials with the desired properties. The central aim of the computer-assisted molecular
and material design techniques is to help the scientists to make the discovery process
faster, cheaper and safer and consequently to foster the industrial research and innovation.
We now have the complete genome sequences of more than 100 organisms and
can employ the tools of bioinformatics to identify genes and proteins as potential drug
targets. The breadth of innovative techniques ranging from fragment-based, analog-based,
structure-based and combinatorial library design allows us to design, synthesize, or screen
for molecules acting on the chosen drug targets more efficiently.
Principles and selected examples of the use of computer-assisted combinatorial
design techniques in the pharmaceutical industry will be presented and discussed. Virtual
library design, focusing, virtual screening as well as pharmacokinetic properties prediction,
will be illustrated on an example of analog-based design of antiviral compounds.
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