Cu(II) complexes based on benzimidazole ligands: synthesis, characterization, DFT, molecular docking &amp; bioactivity study
Creators: name: Hamali, Muhamad Azwan
name: Roney, Miah
name: Dubey, Amit
name: Uddin, Md Nazim
name: Zulkifli, Nur Amira
name: Aluwi, Mohd Fadhlizil Fasihi Mohd
name: Musa, Maslinda
name: Tajuddin, Amalina Mohd
name: Kassim, Karimah
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer

description: <b>Aim:</b> The biggest cause of cancer deaths globally was lung cancer. New cancer fighting drugs are needed due to the rising number of cancer patients and cancer cells' treatment resistance. <b>Results:</b> Two Cu(II) complexes, synthesized from ligands based on 2-aminomethyl benzimidazole and salicylaldehyde derivatives, were designed and evaluated for their effectiveness against A549 lung cancer. The compounds were subjected to computational calculation using Density Functional Theory (DFT) to gather information on their reactivity. Furthermore, molecular docking are utilized to simulate the interaction between the compound and the MPP-9 protein. The synthesis of the ligands and their Cu(II) metal complexes are efficient and straightforward. The complexation between copper atom and the ligand are in 1:1 ratio. The MTT assay of the compounds against A549 lung carcinoma reveals that the both Cu(II) complexes good cytotoxicity activity, in comparison to their respective ligands. The low HOMO-LUMO band gap based on the DFT calculation predicts the high reactivity of the compounds. Furthermore, the low binding energy and the numbers of interactions of the Cu(II) complexes with MMP-9 protein binding site coincide with the antiproliferative activity tested <i>in vitro</i>. <b>Conclusion:</b> The cytotoxicity studies performed for Cu(L1Br) are promising, indicating a good candidate for a future drug. This work aimed to contribute to the discover new anticancer agent by designing a Cu(II) metal complexes based on 2-(aminomethyl)benzimidazole and salicylaldehyde derivatives. Both ligands and their Cu(II) metal complexes were evaluated against A549 lung carcinoma. Furthermore, Density Functional Theory (DFT) using B3LYP 6–311were performed to predict the reactivity of the compounds. Molecular docking between the synthesized compounds and MMP-9 protein was also performed to explore the interactions with the target protein. Cytotoxicity screening of Cu(II) complexes against A549 cell line showed low IC<sub>50</sub> in comparison to their respective ligands, with Cu(L1Br) exhibit the best IC<sub>50</sub> value. The frontier molecular orbitals (FMO) from DFT calculation predict narrow HOMO-LUMO band gap and high softness nature of the Cu(II) complexes indicate a high reactivity of the compounds. Docking simulation of the compounds and targeted protein, MMP-9 show lower binding energy and increase number of interactions by the Cu(II) complexes. This finding correspond with the compounds cytotoxicity activity.