STUDY OF THE OPTICAL PROPERTIES OF 2-THYOHYDANTOIN DERIVATIVES

Smarandache Adriana
1*
Pa!c" A#
1
Andrei I#
1
Hand$%i& 'ad(i)a
2
*iec-*+n+n+(ic$ *a,ar$-na
2

S,aic" An)e%a
1
Pa!c" .#L#
1
1
National Institute for Lasers, Plasma and Radiation Physics, Laser Department, P.O.Box, MG!",
#$$%&', Bucharest, Romania
2
Department of (echnolo)y and Biotechnolo)y of Dru)s,Medical *olle)e, +a)iellonian ,ni-ersity,
*raco., Poland
/mail address for correspondence author0 adriana.smarandache1inflpr.ro
In,r+d"c,i+n/
Lately it is a 2i) challen)e to identify .ays to com2at the failure of treatment of infectious
diseases and cancer, induced 2y multidru) resistance.
In cancer patients, the ma3or mechanism of multidru) resistance is the ele-ated expression of
4(Pdependent dru) efflux pumps, .hich reduce the accumulation of the anticancer a)ents 5%6. In this
respect, there is a need to find ne. dru)s or to manipulate the existin) ones in order to 2rea7 throu)h
multidru) resistance.
4 )roup of chemicals .hose anticancer properties .ere recently studied is the hydantoins
class. 8ydantoin 9&,: ; imida<olidinedione= is a heterocyclic or)anic compound .hich .as o2tained
initially throu)h the reduction of allantoin, a constituent of urine. >ince its synthesis in %?"% 2y Baeyer,
a hu)e num2er of deri-ati-es ha-e 2een prepared 5&6. 4mon) these, se-eral ',';disu2stituted
hydantoins ha-e medical applications as hypnotics and in the treatment of epilepsy as
anticon-ulsants. Dependin) on the nature of su2stitution on the hydantoin rin), these deri-ati-es
possess a .ide ran)e of other pharmaceutical properties, includin) antitumor, antiinflamatory, anti
8I@, hypolipidemic, antiarrhythmic, and antihypertensi-e acti-ities. More than these, recently, the
cytotoxic properties of spyrohydantoin deri-ati-es .ere tested in o-arian and 2reast cancer cells 5!6.
4lso, anticancer effect of Palladium9II= complex of thiohydantoin .as studied on the human colon
carcinoma cell lines 5:6. Aithal, hydantoin, thiohydantoins, and their su2stitution products ha-e many
other uses in a)riculture or industry fields 5'6.
In this study, the optical properties of '9!chloro2en<ylidene=&thioxoimida<olidin:one
9*%#8$*lN&O>, MB&!?."C )Dmol=, )enerically called >E& are presented. 4 sta2ility assay usin)
,@D@I>DNIR spectra .as performed up to &'# days, as .ell as F(IR spectroscopic characteri<ation.
LiGuid samples of >E& in DM>O in 2ul7 .ere exposed to the third harmonic of a pulsed
Nd0H4G laser for different time inter-als. (he 2eha-ior of >E& molecules under laser 2eam influence
.as hi)hli)hted 2ased on their a2sorption spectra 2efore and after coherent li)ht irradiation.
4lso, samples of >E& .ere tested as possi2le photosensiti-e a)ents for photodynamic
therapy throu)h the photochemical method usin) !'' nm Nd0H4G laser 2eam irradiation.
.a,eria%! and me,h+d!
'9!chloro2en<ylidene=&thioxoimida<olidin:one 9*%#8$*lN&O>, MB&!?."C )Dmol=,
)enerically named >E& 9Fi).%= .as synthesi<es at the +a)iellonian ,ni-ersity, *raco., Poland and
7indly pro-ided 2y Dr. +ad.i)a 8and<li7, and Prof. Iatar<yna IiecIonono.ic<#
Fi).%. !D chemical structure of >E&, .here the car2on atoms are cyan, the hydro)en atoms are li)ht
)ray, the chloride atom is )reen, the nitro)ens are 2lue, oxy)en is red and sulfur is yello..
(he compound .as dissol-ed into DM>O sol-ent 9purchased from Merc7= in a concentrations ran)e
2et.een %#
'
M and %#
!
M. (here .ere three )roups of solutions, that .ere 7ept in the follo.in)
conditions0 at :
#
* in dar7, at &&
#
* in dar7, and at &&
#
* in am2ient li)ht.
>olutions of >E& .ere characteri<ed 2y F(IR spectroscopy method, usin) the Nicolet I>'#
F(IR spectrophotometer 9(hermo >cientific, ,>4= ha-in) #.#C cm
%
resolution, .ith Omnic C >tandard
soft.are.
>ta2ility study of >E& solutions in DM>O .as performed up to &'# days in Guart< cells of
#.% cm optical path usin) an ,@D@I>DNIR spectrophotometer 9Lam2da C'#, Per7in /lmer, ,>4=, .ith
less than #.#' nm resolution for ,@D@I> domain and less than #.& nm for NIR spectral ran)e. (he
cumulated measurin) errors limit is %.#:'J, .hich contains the measurin) error limit of the
spectrophotometer, and the cells positionin) error 5"6.
4 % cm
!
-olume of >E& solution %#
:
M in DM>O .as irradiated .ith laser 2eam emitted at !''
nm 2y a pulsed Nd0H4G laser 9Surelite II, Excel Technology, Continuum, USA) up to !# min. (he
output laser 2eam .as directed to the sample Guart< cell throu)h a ,G' optical filter in order to cutout
the residual '!& nm radiation. %#J of emitted 2eam .as splitted to a po.ermeter 9K/&' Gentec,
*anada= for monitorin) the 2eam ener)y on the sample cell. (he laser radiation had the follo.in)
characteristics0 %# pps ; pulse repetition rate, ' ns ; F(A8M, and the 2eam ener)y on the sample ;
!? m+.
>in)let oxy)en .as )enerated 2y photoexcitation on the >E& molecules .ith laser pulses at
!''nm, too, follo.ed 2y the ener)y transfer 2et.een the triplet state of >E& and the )round state of
the sol-ated O& molecules. (ime resol-ed phosphorescence of sin)let oxy)en 9at B%&$# nm= .as
measured 2y usin) a cooled NIR photomultiplier 98amamatsu 8%#!!#, +apan=, .hose output .as
coupled to a di)ital scope 9(e7tronix DPO $&$:, ,>4=. (he experimental setup .as descri2ed in
detail else.here 5$6.
Re!"%,! and di!c"!!i+n!
(he a2sorption spectrum of >E& in DM>O 9Fi).&= is characteri<ed 2y a 2road 2and in ,@
spectral ran)e .ith a2sorption pea7s at &C: nm, !"! nm and !$C nm. 4lso, a sharp a2sorption
maxima stands out in ,@*, at &:" nm and a 2road -ery .ea7 2and in @I> at ::! nm. In NIR it can 2e
o2ser-ed a pea7 centered at %C:# nm.
Re0erence!/
5%6 (ur7 D. and ><a7acs G., Rele-ance of multidru) resistance in the a)e of tar)eted therapy. *urr.
Opin. Dru) Disco-. De-el. 12(2)0 &:"&'&, &##C.
5&6 4-endano *. and Nenende< +. *., 8ydantoin and Its Deri-ati-es in Iir7Othmer /ncyclopedia of
*hemical (echnolo)y, Ailey, &###.
5!6 Ra3ic E., Eorc B., RaicMalic >., /ster I., Iral3 M., Pa-elic I., Bal<arini +., De *lercG /., and Mintas
M., 8ydantoin deri-ati-es of L and Damino acids0 synthesis and e-aluation of their anti-iral and
antitumoral acti-ity. Molecules 11(11)0 ?!$?:?, &##".
5:6 >mit B., Pa-lo-ic R., Radosa-l3e-icMihailo-ic 4., Dosen 4., *urcic M., >e7lic D. and Ei-ano-ic
M., >ynthesis, characteri<ation and cytotoxicity of a palladium9II= complex of !59&hydroxy
2en<ylidene=amino6&thioxo imida<olidin:one, +. >er2. *hem. >oc. 77 (0): %;%', &#%&.
5'6 Ware E., The Chemistry of the y!antoins, Chem. "e#. 46(3): $%& ' $(%, )*+%.
5"6 Militaru 4., >marandache 4., Mahamoud 4., 4li2ert >., Pa)Ls +.M. and Pascu M.L., (ime >ta2ility
>tudies of Kuina<oline Deri-ati-e Desi)ned to Fi)ht Dru) Resistance 4cGuired 2y Bacteria, Letters
in Dru) Desi)n M Disco-ery, 8: %&:%&C, &#%%.
5$6 >taicu 4., Pascu 4., Boni M., Pascu M.L., /nescu M., Photophysical study of En phthalocyanine in
2inary sol-ent mixtures, +ournal of Molecular >tructure0 doi%s&.#>##&&&?"#%&#%%"#N, &#%!.