Transcript Diapositiva 1

Solubility profile assessment of some new anticancer
compounds
George Mihai Nițulescu, Bruno Ștefan Velescu, Georgiana Nedelcu,
Octavian Tudorel Olaru
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Objectives
Absorption, distribution and elimination of drugs
are properties that depends on the solubility in the
biological fluids. Water solubility represents a
prerequisite in the drug development and can predict
the drug behavior in various pH media. In silico
procedures are useful tools for the prediction of water
solubility and represents a starting point in the
solubility determination. However the correlation
between predicted and experimental results should
be investigated for new compounds. Solubility in
various pH media is helpful in predicting the
bioavailability and in the development of the
dissolution method.
In the present study, we use in silico methods to
predict water solubility of six pyrazole compounds
with anticancer action. Thereafter we determined the
solubility in water and in four different media.
Material and methods
Solubility of six pyrazole compounds was was
determined in water and in four USP media: 1.0, 4.5 6.8
pH buffer and 0.1% sodium dodecyl sulfate. The
determinations
were
performed
by
UV-VIS
spectroscopy.
Fig 2. UV-VIS
compounds
spectra
of
the
new
H
N N
S
BT2, R=H
O
H3C
N
H
BM2, R=CH3
N
H
R
S
O
BC2, R=Cl
BT3, R=H
N
N
H3C
N
H
N
H
BM3, R=CH3
R
BC3, R=Cl
Fig 1. The structures of the new anticancer
pyrazole compounds
Results
Compound BT3 has shown the highest water
solubility and BC2 the lowest in both in silico and
experimental determinations. The experimental and
predicted results showed a good correlation degree
(r2=0.9385) (fig.3). pH 1.0 media did not influenced
the solubility for the compounds BT2, BC3 and BT3,
but slightly improve it for BC2 and decrease it for BM2
and BM3. With the exception of BM3 in which the
solubility was increased slightly, the 6.8 pH buffer
decrease significant the solubility. The 4.5 pH buffer
has decreased the solubility of BC2, BM2 and BT2 an
did not influence the solubility of BC3, BM3 and BT3.
0.1% sodium dodecyl sulfate improve the solubility of
all compounds.
pyrazole
Conclusions
Solubility of six pyrazole compounds was assessed
by UV-VIS spectrophotometry. The experimental and
predicted solubilities showed a good correlation degree.
Acknowledgments
The authors acknowledge the financial support offered
by the National Authority for Scientific Research of Romania,
through UEFISCDI grant PN-II-RU-TE-2011-3-0228.
Fig 3. Correlation degree of predicted versus
experimental solubility in aqueous media (pH=7)