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

• Main Authors: Alberto Aragón-Muriel, Yamil Liscano, Yulieth Upegui, Sara M. Robledo, María Teresa Ramírez-Apan, David Morales-Morales, Jose Oñate-Garzón, Dorian Polo-Cerón
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Antibiotics
• Subjects: metal-based drugs; antiproliferative activity; antibacterial activity; antiparasitic activity; model membranes; molecular docking
• Online Access: https://www.mdpi.com/2079-6382/10/6/728

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 (1<i>H</i>-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 <i>Leishmania braziliensis</i>, <i>Plasmodium falciparum,</i> and <i>Trypanosoma cruzi</i>. Additionally, antibacterial activities were examined against two Gram-positive strains (<i>S. aureus</i> ATCC^® 25923, <i>L. monocytogenes</i> ATCC^® 19115) and two Gram-negative strains (<i>E. coli</i> ATCC^® 25922, <i>P. aeruginosa</i> 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), <i>P. falciparum</i> alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and <i>S.</i><i>aureus</i> 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.