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Abstract Various sets of thiazole, thiophene, and 2-pyridone ring structures containing a dimethylaniline component were synthesized. Substituted thiazoles 2 – 3 and thiophenes 5 – 7 were produced by reacting thiocarbamoyl compound 4 with α-halogenated reagents in different basic conditions. Also, a series of 2-pyridone derivatives 9a – f substituted with dimethylaniline was synthesized through Michael addition of malononitrile to α,β-unsaturated nitrile derivatives 8a – f . The synthesized products were structurally proven by spectroscopic methods such as IR, 1 H NMR, 13 C NMR, and MS data. Furthermore, the anti-cancer efficacy of the compounds was assessed using the MTT assay on two cell lines: hepatocellular carcinoma ( HepG-2 ) and breast cancer ( MDA-MB-231 ). The results showed the highest growth inhibition for derivatives 2 , 6 , 7 , and 9c , which were further examined for their IC 50 values. The IC 50 for compound 2 showed equipotent activity (IC 50 = 1.2 µM) against the HepG-2 cell line compared to Doxorubicin (IC 50 = 1.1 µM). Compounds 2 , 6 , 7 and 9c showed very good ADME assessments for further drug administration. Moreover, the PASS theoretical prediction for the compounds showed high antimitotic and antineoplastic activities for compounds 2 , 6 , 7 , and 9c , as well as potent inhibition activity for the insulysin enzyme (IDE). Molecular docking stimulations were performed on CDK1/CyclinB1/CKS2 (PDB ID: 4y72) and BPTI (PDB ID: 2ra3). When docked into (PDB ID: 4y72), all of the tested compounds showed considerable inhibition, and the 2-pyridone derivative 9d had the maximum binding affinity (− 8.1223 kcal/mol). While thiophene derivative 6 offered the maximum binding affinity (− 7.5094 kcal/mol) when docked into (PDB ID: 2ra3). Graphical Abstract
Metwally et al. (Thu,) studied this question.