Synthesis, characterization, and biological activity using computational study of synthesized monocyclic β-lactam ligands

The synthesis of monocyclic β-lactam ligands, their spectral as well as the X-ray crystallographic analysis, computational study, and biological activity are all covered in this article. The characterization of all these ligands is completed through FT-IR, 1H NMR, 13C NMR and X-ray crystallography study. We applied computational study to analyze the biological activity of all the designed monocyclic β-lactam ligands (4a, 4b, 4c and 4d) against cancer. For this purpose, ligand-protein interactions are studied by molecular docking and quantum chemical computations. The frontier molecular orbitals (FMOs) results show a clear intramolecular charge transfer from central core (azetidine) towards thiadiazole ring more like donor and acceptor groups. Molecular electrostatic potentials (MEPs) are visualized to get insights to electrophilic and nucleophilic regions of studied compounds with the help of specific color codes. We calculated and compared bond lengths, bond and torsional angles for optimized geometry of 4a using M06-2X functional and 6-311G++(d, p) basis sets. The matrix metalloproteases (MMP-9) protein which actively causes proliferation of cancer cells. Molecular docking results indicate that ligands 4a, 4b, 4c and 4d show the maximum binding energies (B.E) of − 9.0, − 9.4, − 7.8 and 9.0 kcal.mol −1 with MMP-9 protein. The studied 2-D and 3-D interactions show that compound 4b and 4d interact more vigorously with MMP-9 protein. For compound 4a, density of states (DOS) plot is calculated by dividing the molecule into three fragments. DOS results provide the major contributions of fragments containing thiadiazole ring towards HOMO and LUMO at ~ − 13 eV to 5 eV, respectively. According to the results of molecular docking of synthesized compounds, three hydrogen bonds were involved in the interaction with MPP-9. The outcomes of molecular docking calculations not only support the biological activity and interaction behavior of all studied ligands with MPP-9, but also indicate a potential use in electro-optical applications. The current investigation highlights the importance of the entitle compounds as efficient bioactive candidates against cancer as investigated through experimental and quantum computational techniques.