In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

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.

A Review on the Antimicrobial Activity of Schiff Bases: Data Collection and Recent Studies

“…A recent study by Aragón-Muriel et al (2021) [ 62 ] investigated the antibacterial potential of four benzimidazole-based Schiff bases and their metal complexes against two Gram-positive strains ( S. aureus 25923, Listeria monocytogenes 19115) and two Gram-negative strains ( E. coli 25922, P. aeruginosa 27583). As generally observed, the activity of the complexes was higher than that of SBs alone.…”

“…Moreover, isomerism in SBs seemed to play a crucial role, as is often the case for compounds with biological activity [ 63 ]. The major activity found in the study by Aragón-Muriel et al (2021) [ 62 ] was shown by 34 and 35 (MIC = 250 ng/mL against S. aureus versus 0.5 ng/mL of ciprofloxacin). Despite the low activity of SBs, this study provided novel insights into the mechanisms through which the compound exerts antibacterial action, suggesting that interactions with the bacterial membrane or interactions with DNA could be involved.…”

Synthesis of Benzimidazole-Sulfonyl Derivatives and Their Biological Activities

“…In this feature, benzimidazole anchored sulfonamide moiety has a substantial role in the bioactive compounds. Benzimidazole derivatives have developed a considerable interest in the medical field due to their therapeutic action as antimicrobial [ 3 – 6 ], antitumor [ 7 – 10 ], antihelmintic [ 11 ], antihistaminic [ 12 – 14 ], proton pump inhibitors [ 12 , 15 ] anti-inflammatory [ 16 – 18 ], anticancer [ 19 ], antioxidant [ 20 ], and antihypertensive [ 21 ] drugs. Benzimidazole anchored with other heterocyclic compounds, such as triazole, thiadiazole, oxadiazole, morpholine, piperazine, or piperidine, has exhibited potential bioactivities [ 22 , 23 ].…”

Synthesis, Characterization, Anti-tubercular Evaluation, and Teratogenicity Studies of Novel 5-(4-fluorobenzoyl) tetrahydro benzamidazoquinazoline Derivatives

“…The creation and development of drugs with broad applicability in the pharmaceutical industry nowadays heavily relies on heterocyclic molecules. The therapeutic effects of benzimidazole derivatives as antibacterial, 5,6 antitubercular, [7][8][9] antitumor, 10 anthelmintic, 11 antihistaminic, 12 proton pump inhibitors, 12 anti-inflammatory, 13 anticancer, 14 antioxidant, 15 and antihypertensive 16 drugs have generated a great deal of attention in the medical community. Quinazolines serve as the building blocks for creating a variety of biologically active compounds and have played significant roles in medicinal chemistry.…”