Structure-activity relationship of 15 different Mn-salen derivatives against free radicals

Abstract

Increased levels of reactive oxygen species (ROS) play a vital role in the pathogenesis of various diseases. Thus, antioxidants would play pivotal roles in the therapy of ROS-induced diseases. Regarding this fact, in the present study, we compared the relative scavenging potency and cytoprotective effects of 15 Mn-salen complexes (EUKs: eukarion antioxidant compounds), having different substituted groups, against induced free radicals (O₂^˙–, H₂O₂, ^˙OH, and ABTS^˙+) and protein carbonylation (PCO) in vitro as well as H₂O₂-induced damages and lipofuscin production in cellular systems. The results revealed that all Mn-salen complexes had considerable effects on O₂^˙–, H₂O₂, and ^˙OH scavenging, relative to common antioxidants, in a concentration-dependent manner. Further, our data demonstrated that the nature and position of different substitutions on the salen ring had significant effects on scavenging activity, PCO formation, as well as suppression of cytotoxicity and apoptosis induced in cells by H₂O₂. Among studied complexes, EUK-15 and -123 showed the most catalase and superoxide dismutase activities, whereas their ^˙OH-scavenging activities were very weak. The cytoprotective effects of the salens, mainly EUK-15 and -123, were also associated with a significant reduction in the extent of intracellular lipofuscin pigments. Evaluation of the 15 salen derivatives clearly indicated these compounds possess ROS-scavenging activity and this activity is potentiated by the presence of para and ortho alkoxy groups.

Keywords::

• Antioxidant
• cytotoxicity
• Mn-salen complexes
• protein oxidation
• reactive oxygen species
• SK-N-MC cells