Abstract
Background and Objective:
Due to the well-documented anti-proliferative activity of
2-thiohydantoin incorporated with pyrazole, oxadiazole, quinazoline, urea, β-naphthyl carbamate and
Schiff bases, they are noteworthy in pharmaceutical chemistry.
Methods:
An efficient approach for the synthesis of a novel series of 2-thiohydantoin derivatives incorporated
with pyrazole and oxadiazole has proceeded via the reaction of the acyl hydrazide with
chalcones and/or triethyl orthoformate. Schiff bases were synthesized by the reaction of the acyl hydrazide
with different aromatic aldehydes. Moreover, Curtius rearrangement was applied to the acyl
azide to obtain the urea derivative, quinazoline derivative, and carbamate derivative.
Results:
The synthesized compounds structures were discussed and confirmed depending on their
spectral data. The anticancer activity of these heterocyclic compounds was evaluated against the breast
cancer cell line (MCF-7), where they showed variable activity. Compound 5d found to have a superior
anticancer activity, where it has (IC50 = 2.07 ± 0.13 μg/mL) in comparison with the reference drug
doxorubicin that has (IC50 = 2.79 ± 0.07 μg / mL). Then compound 5d subjected to further studies such
as cell cycle analysis and apoptosis. Apoptosis was confirmed by the upregulation of Bax, downregulation
of Bcl-2, and the increase of the caspase 3/7percentage.
Conclusion:
Insertion of pyrazole, oxadiazole and, quinazoline moieties with 2-thiohydantoin moiety
led to the enhancement of its anti-proliferative activity. Hence they can be used as anticancer agents.