N-Alkylation Hybrids: Synthesis, Characterization, Anticancer Properties and Computational Insights

A series of (E)-2-(2-(anthracen-9-ylmethylene)hydrazinyl)-4-(pyrrolidin-1-ylmethyl)thiazole (7a-l) were synthesized and evaluated for their in vitro anticancer activity against three human cancer cell lines of MCF-7 (breast), A549 (lung) and HepG2 (liver). In this study, cisplatin served as the positive control. The results showed that the synthesized compounds 7c, 7g, 7i, 7j and 7l demonstrated promising activity against all three cancer cell lines. Notably, compound 7j exhibited higher activity than the standard drug cisplatin against MCF-7, A549 and HepG2, with IC50 values of 9.08 ± 0.32 µM, 5.92 ± 1.16 µM and 6.96 ± 0.13 µM, respectively. Molecular docking studies of the compounds 7g, 7i and 7j with DNA topoisomerase II (PDB ID:3QX3) indicated strong affinity toward the target protein. Moreover, an in silico pharmacokinetic profile was generated for compounds 7g, 7i and 7j using SWISS/ADMET and pkCSM. Furthermore, compounds 7g, 7i and 7j were found to comply with the Lipinski, Ghose, Veber, Egan and Muegge rules. Based on the results, compound 7j was characterized by and density functional theory (DFT) studies.