Affiliation:
1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig, University, Zagazig, 44519, Egypt
2. Mansoura University Hospital, Mansoura University, Mansoura, Egypt
3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
4. Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
Abstract
Aim:
pyrimidine and pyrazole have various biological and pharmaceutical applications
such as antibacterial, antifungal, antileishmanial, anti-inflammatory, antitumor, and anti-cancer.
Introduction:
In this search, the goal is to prepare pyrimidine-pyrazoles and study their anticancer
activity.
Methods:
1-allyl-4-oxo-6-(3,4,5-trimethoxyphenyl)-1,4-dihydropyrimidine-5-carbonitrile bearing pyrazoles (4,6-8) have been synthesized. Firstly, the reaction of 1-allyl-2-(methylthio)-4-oxo-6-(3,4,5-trimethoxyphenyl)-1,4-dihydropyrimidine-5-carbonitrile (1) with chalcones 2a-b produced the intermediates 3a-b. The latter was reacted with hydrazine hydrate to give the targets 4a-b. On the other hand, hydrazinolysis of compound 1 yielded the hydrazino derivative 5 which upon reac-tion with chalcones 2c-i or 1,3-bicarbonyl compounds afforded the compounds 6-8. Finally, the new compounds were characterized by spectral data (IR, 1H NMR, 13C NMR) and elemental analysis. Moreover, they were evaluated for Panc-1, MCF-7, HT-29, A-549, and HPDE cell lines as anti-cancer activity.
Results:
All the tested compounds 3,4,6-8 showed IC50 values > 50 μg/mL against the HPDE cell line. Compounds 6a and 6e exhibited potent anticancer activity where the IC50 values in the range of 1.7-1.9, 1.4-182, 1.75-1.8, and 1.5-1.9 μg/mL against Panc-1, MCF-7, HT-29, and A-549 cell lines.
Conclusion:
New pyrimidine-pyrazole derivatives were simply synthesized, in addition, some of them showed potential anticancer activity.
Funder
deanship of scientific research (DSR) at King Abdulaziz University (KAU), Jeddah, Saudi Arabia
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Biochemistry