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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. Method: 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.

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