Abstract
Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S. aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.
Highlights
In medicinal chemistry, a large number of studied coordination compounds have demonstrated biological properties
Schiff bases derived from benzimidazoles are quite attractive for medicinal chemistry applications due to the broad biological activity of the benzimidazole ring [8], which has been characterized with antitumor, antimicrobial, antiulcerative, anti-inflammatory, antihypertensive, and antiviral activities [9,10,11]
All compounds were characterized by mass spectrometry (MS), elemental analyses (C, H, and N), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy
Summary
A large number of studied coordination compounds have demonstrated biological properties. When choosing organic ligands for coordination with metallic centers, the compounds should present different coordination points that may exhibit biological activity [5]. Schiff bases are known as privileged ligands because they are easy to obtain and can form multidentate complexes with various metallic centers due to the presence of donor heteroatoms, which generally appear in their structures as nitrogen and oxygen molecules [6,7]. Schiff bases derived from benzimidazoles are quite attractive for medicinal chemistry applications due to the broad biological activity of the benzimidazole ring [8], which has been characterized with antitumor (bendamustine), antimicrobial (albendazole), antiulcerative (omeprazole), anti-inflammatory (benoxaprofen analog), antihypertensive (candesartan), and antiviral (enviradine) activities [9,10,11]. In silico tests performed on the FPK protein showed that benzimidazole derivatives are likely to inhibit the glycolysis cycle in Trypanosoma cruzi, resulting in antiparasitic activity [18]
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