MedChemComm
Research Article
lar to A, with no improvements at 100 or 250 μM. The inhibi-
tion of cell viability by B at 500 μM is weaker than that by
molecule A, which shows a value of 84% regarding the same
aspect. All other tested compounds do not show significant
effects 48 hours after the treatment. The isomeric mixture M
is more active than the trans isomer D at all the four used
concentrations, even after 48 hours from the treatment.
Finally, we performed a preliminary stability test on more
active molecules A and B and on the natural molecule X.
These compounds were allowed to stay in their pure form at
room temperature (an average of 298.15 K) for one week. Af-
1
ter this period the purity was checked and confirmed by H-
NMR spectroscopy. Small quantities of A, B, and X were
dissolved in deuterated chloroform and these samples were
left to stand at room temperature (an average of 298.15 K) for
one week. After this period, the acceptable purity was
Fig. 1 Percentage of cell viability 24 hours after the treatment.
1
checked and confirmed by H-NMR spectroscopy for the syn-
thetic compounds A and B, while for the natural molecule X
a significant change of purity was evident from the spectrum
(molecule X was estimated to be 40% pure by chromatogra-
phy). This test can be useful for more advanced studies with
medicinal interests. Unsaturated organosulfur compounds
are widespread in nature, mostly thanks to the plants of ge-
nus Allium. These compounds are observed as promising
pharmacologically active molecules, but the relationship be-
tween the structure and the activity is still not clear. In this
work, we synthetized and tested the in vitro anti-tumor poten-
tial of different unsaturated disulfides using human adeno-
carcinoma cells. From the data collected and reported above,
we can conclude that unsaturated disulfides hold promise for
the inhibition of the cell viability of the A549 cell line. For
the first time, the DADS analogues A and B have been proven
to be more active on a cancer cell line than the natural mole-
cule diallyl disulfide. In addition, the unsaturation site is not
the principal driving force, but other factors, like the size of
the molecule and the length of the carbon chain, can be im-
portant guidelines for more advanced studies in this field in
future.
Fig. 2 Percentage of cell viability 48 hours after the treatment.
different isomeric forms triggered a slight decrease in cell vi-
ability only at the highest concentration (500 μM). The iso-
meric mixture M is more active than the trans isomer D at all
the four used concentrations, probably due to the higher per-
centage of the cis isomer. The loss of the anti-tumor activity
was also observed for molecule E, which had a terminal dou-
ble bond on its carbon chain. These results indicate that the
carbon chain length is likely to play a more active role in the
potential anti-tumor activity of such unsaturated compounds.
After 48 hours of incubation (Fig. 2), molecules X, A, and
B show a significant and time-dependent in vitro anti-tumor
activity. These two synthetic derivatives of DADS generate
stronger effects at all the four used concentrations. The lead
molecule X induces 54% viability inhibition at 50 μM. Mole-
cule A induces a viability inhibition of 68% at the same con-
centration. Molecule B has a similar effect, with 70% viability
inhibition at 50 μM. For molecule X, the percentage inhibi-
tion doesn't change significantly from 50 to 250 μM, and
reaches almost the same activity as that of the synthetic ana-
logues at 500 μM, with 65% inhibition overall. Molecule A
shows a concentration-dependent activity while passing from
50 μM to 100 μM, while no significant changes are observed
at 250 μM. Almost complete inhibition was observed for mol-
ecule A at 500 μM. Compound B at 50 μM shows effects simi-
Conflicts of interest
There are no conflicts to declare.
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