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Design, Synthesis, and Anticancer Potential of the Enzyme (PARP-1) Inhibitor with Computational Studies of New Triazole, Thiazolidinone, - Thieno [2, 3-d] Pyrimidinones

[ Vol. 17 , Issue. 6 ]


Ameen A. Abu-Hashem*, Khadiga M. Abu-Zied, Magdi E.A. Zaki, Mohamed F. El-Shehry , Hanem M. Awad and Mohammed A. Khedr   Pages 807 - 825 ( 19 )


Background: Thienopyrimidine, triazole and thiazolidinone derivatives have recently gained attention due to their effective pharmacological activities. They show antioxidant, antitumor, antimicrobial, antiviral, anti-inflammatory and analgesic properties.

Objective: Synthesis of new ethyl 2-amino-4-isopropyl-5-methylthiophene-3-carboxylate (2) was used as a starting material to produce 2-mercapto-methylthienopyrimidinone (3), (4) and 2- hydrazinyl-methylthienopyrimidinone (5), through high yields and evaluating anticancer activities.

Methods: A series of novel Schiff's bases (6-9) were produced after treatment of (5) with aldehydes. Triazolopyrimidinones (6a, 7a, 8a, 9a) were produced from cyclization of benzylidene (6-9) using Br2 / AcOH or dry pyridine /Ac2O. Thiazolidinones (6b, 7b, 8b, 9b) were synthesized from benzylidene (6-9) with mercaptoacetic acid.

Results: All the compounds were synthesized in good yields (55-85%) in a regularly actual system under mild condition. The new compounds have been established by means of diverse spectroscopic ways as IR, NMR and MS. The newly synthesized compounds were evaluated for their antiproliferative activity against the breast MCF-7 carcinoma cell line. Compound (7) showed promising anticancer activity with IC50 of 6.9 μM, and 40.8% of antioxidant effect as DPPH inhibition. Molecular docking of (7) showed ΔG values of-20.54 kcal/ mol and -25.60 kcal/ mol. Molecular dynamics simulation of (7) in complex with PARP-1 revealed RMSD of 3.00 Ǻ.

Conclusion: The QSAR study confirmed the presence of a relationship between anticancer activity and subdivided surface area descriptors with coefficient r2 = 0.98 with high predictive power.


Pyrimidines, thienopyrimidines, triazolopyrimidinones, thiazolidinones, anticancer, antioxidant, molecular docking, molecular dynamics, QSAR.


Photochemistry Department (Heterocyclic Unit), National Research Centre, Dokki, Giza 12622, Photochemistry Department (Heterocyclic Unit), National Research Centre, Dokki, Giza 12622, Photochemistry Department (Heterocyclic Unit), National Research Centre, Dokki, Giza 12622, Pesticide Chemistry Department, National Research Centre, Dokki 12622, Cairo, Department of Tanning Materials and Leather Technology, National Research Centre, Dokki 12622, Cairo, Pharmaceutical Chemistry Departments, Faculty of Pharmacy, Helwan University, Ein Helwan 11790,Cairo

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