Objective: Anticancer activities of Schiff bases S1 and S2 against MG-63 human osteosarcoma cells were performed and described using an in vitro evaluation employing cytotoxicity and apoptosis assay. Methods: MG-63 cells were used in an MTT assay to examine the effect of the compound on cell viability (S1 and S2). Cell morphologies and IC50 values were obtained. The acridine orange (AO)/ethidium bromide (EB) dual staining technique was used to determine the apoptosis process. Results: Our findings showed that synthesised S1 and S2 reduced MG-63 cell proliferation and induced apoptosis in a dose-dependent manner, implying that they could be used to treat bone cancer. Conclusion: Our findings showed that synthesised S1 and S2 reduced MG-63 cell proliferation and induced apoptosis in a dose-dependent manner, implying that they could be used to treat bone cancer.

Following mechanical milling, the condensation reaction of the corresponding heterocyclic aldehydes with Isoniazid yields the Schiff base (E)‐N′‐((1H‐pyrrol‐2‐yl) methylene)isonicotinohydrazide (S1) and (E)‐N′‐(Thiophen‐2‐ylmethylene)isonicotinohydrazide (S2) supported heterocyclic derivatives. The structures of the Schiff bases, S1 and S2 were confirmed by 1H NMR, 13C NMR and IR spectroscopy. Copper ions (Cu2+) were trapped by S1 in DMSO to form the yellow‐coloured complex Cu‐(E)‐N′‐((1H‐pyrrol‐2‐yl)methylene) isonicotinohydrazide (Cu2++S1) with high sensitivity and selectivity. But the same ligand S1 could not be able to capture other metal ions tested for this work (namely, Co2+, Ni2+, Zn2+, Mn2+, Hg2+, Cd2+, Pb2+, Fe2+, and Fe3+) in DMSO. UV‐visible spectroscopic results confirmed the complex formation (Cu2++S1) with copper ions, but not with the other ions. Analysis of non‐covalent interactions (NCI) of ligand S1 with Ni2+, Cu2+ and Zn2+ in DMSO were investigated by density functional theory (DFT). NCI analysis of S1 by Cu2+ ions in DMSO was in good agreement with the experimental results. S2 did not react with any metal ions used in this study to form a complex in DMSO and the same was confirmed by UV‐Visible spectra. Reasonably good antibacterial activity was observed with S1, S2, Cu2++S1 compared to amoxicillin against Gram‐negative bacteria (K. pneumoniae, E. coli), Gram‐positive bacteria (S. aureus, S. pneumoniae), and fungal strain (C. albicans).