Sayed Fatma Nabil, Omar Norhan Refaie, Mahmoud Nessma Fathi, Mohamed Gehad Genidy
Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt.
Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt.
J Trace Elem Med Biol. 2024 Dec;86:127502. doi: 10.1016/j.jtemb.2024.127502. Epub 2024 Jul 29.
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 H-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).
氨溴索（BHX）是一种黏液溶解剂，用于治疗与过多或黏稠黏液相关的呼吸系统疾病。据报道，过渡金属配合物在治疗多种人类疾病方面取得了巨大进展。人们正在大力开发过渡金属配合物作为药物。金属配合物可以形成多种配位几何结构，使其具有独特的形态。因此，已制备了氨溴索药物的二元金属配合物，以提高游离药物的生物活性和稳定性。
用一些过渡金属离子，即Cr(III)、Mn(II)、Fe(III)、Co(II)、Ni(II)、Cu(II)、Zn(II)和Cd(II)，制备了一系列新的与氨溴索药物（BHX）的二元配合物。通过元素分析、傅里叶变换红外光谱（FT-IR）、质谱、热分析和紫外可见光谱对所制备的金属配合物进行了表征和结构解析。测试了配体和金属配合物对多种致病细菌（枯草芽孢杆菌、大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌）的抗菌活性。此外，与二元金属配合物不同，还测试了该配体对MCF-7乳腺癌细胞系的抗癌疗效。利用分子对接研究确定了游离BHX配体和Co(II)配合物在大肠杆菌（PDB ID：3T88）和铜绿假单胞菌（PDB ID：6NE0）晶体结构蛋白活性区域的结合方向或构象。
根据FT-IR和H-NMR光谱结果，BHX配体以中性双齿模式与金属离子配位。配合物在N,N-二甲基甲酰胺（DMF）中的摩尔电导率测量证明了所有二元配合物的电解质性质。Co(II)配合物对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌的抑菌圈直径最大。Zn(II)配合物对铜绿假单胞菌和枯草芽孢杆菌的抑制作用最强。此外，Cd(II)螯合物作为抗铜绿假单胞菌和金黄色葡萄球菌的抗菌剂表现出高效性。
所有输出数据共同证实了金属配合物的八面体几何结构。生物学研究结果表明，金属配合物可能比游离BHX配体更具活性。对于MCF-7细胞系，Cd(II)-L配合物是高活性配合物（4.95 µg/mL），但游离BHX药物是最具活性的化合物（3.96 µg/mL）。
