Bidentate bromhexine drug coordination modes with various transition metal ions: Synthesis, characterization, and in vitro antibacterial and anti-breast cancer activity tests

• Published in: Journal of trace elements in medicine and biology 2024-12, Vol.86, p.127502, Article 127502
• Main Authors: Sayed, Fatma Nabil, Omar, Norhan Refaie, Mahmoud, Nessma Fathi, Mohamed, Gehad Genidy
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anticancer activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; BHX binary complexes; Breast Neoplasms - drug therapy; Cell Proliferation - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Drug Screening Assays, Antitumor; Escherichia coli - drug effects; Female; FT-IR and 1H NMR; Humans; Ions - chemistry; MCF-7 Cells; Microbial Sensitivity Tests; Molecular docking; Pathogenic bacterial species; Pseudomonas aeruginosa - drug effects; Staphylococcus aureus - drug effects; Thermal study; Transition Elements - chemistry; Transition Elements - pharmacology
• ISSN: 0946-672X; 1878-3252; 1878-3252
• DOI: 10.1016/j.jtemb.2024.127502

Bromhexine (BHX) is a mucolytic drug used in treatment the respiratory disorders which are associated with excessive or viscid mucus. Transition metal complexes have made tremendous progress in the treatment of a variety of human ailments, according to reported articles. Transition metal complexes are being developed as medications with a lot of effort. Metal complexes can form a variety of coordination geometries, giving them distinct forms. So, binary metal complexes of bromhexine drug have been prepared to enhance the biological activity and stability of the free drug. A new series of binary complexes with bromhexine drug (BHX) has been prepared with some transition metal ions namely Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II). Elemental analyses, FT-IR, mass spectrometry, thermal studies and UV-Vis spectra have been used to characterize and structurally elucidate the produced metal complexes. Antibacterial activity has been tested for the ligand and metal complexes against a variety of pathogenic bacterial species (Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus). In addition, the ligand has been tested for anticancer efficacy against the MCF-7 breast cancer cell line, as opposed to binary metal complexes. The binding orientation or conformation of the free BHX ligand and Co(II) complex in the active region of the protein of crystal structure of Escherichia coli (PDB ID: 3T88) and Pseudomonas aeruginosa (PDB ID: 6NE0) has been performed using molecular docking studies. The BHX ligand coupled in neutral bidentate mode to the metal ions, according to FT-IR and 1H-NMR spectral results. The molar conductivity measurements of the complexes in DMF proved the electrolytic nature of all binary complexes. Co(II) complex showed the highest inhibition zone diameter against S. aureus, E. coli and P. aeruginosa. Zn(II) complex had the greatest inhibitory effect against P. aeruginosa and B. subtilis. Also, Cd(II) chelate appeared high efficacy as antibacterial agent against Pseudomonas aeruginosa and Staphylococcus aureus. All the output data conjugated to confirm the octahedral geometry of the metal complexes. The biological findings revealed that metal complexes can be more active than the free BHX ligand. Against MCF-7 cell line, Cd(II)-L complex is highly active complex (4.95 µg/mL) but BHX free drug is the most active compound (3.96 µg/mL).