title: 3-methoxy aroylhydrazones - free radicals scavenging, anticancer and cytoprotective potency.
abstract: OBJECTIVE
  This study aimed to determine the capability of newly designed 3-methoxy derivatives of salicylaldehyde benzoylhydrazone to influence the oxidative stress processes and to test their in vitro cytotoxicity.
  
  
  METHODS
  We have used chemiluminescent and spectrophotometric model systems containing different types of reactive oxygen species (OH●, OCl─and O2─●). The hydrazones effect on the viability of Hep-G2, HEK-293 and SH-SY5Y cell lines was determined via MTT assay.
  
  
  RESULTS
  The comparative analysis of the C50values of the chemiluminescent investigation demonstrated moderate activity against the hydroxyl radicals (C50> 50 μmol/L) and remarkable reactivity in the systems containing a superoxide radical and a hypochlorous anion (C50< 3.7 μmol/L). Further experiments in the spectrophotometric system of UV-induced OH●generation and consequent 2'-deoxyribose oxidative damage excluded the possibility of quenching effect and proved the direct interaction of the studied compounds with that generated in the system reactive oxygen species (ROS). The encapsulation of the studied derivatives into chitosan-alginate particles led to the protection and stabilization of their antioxidant activity as revealed by a one-month study using the ABTS●+method. The cytotoxic study revealed less pronounced effects against the non-malignant cell line (HEK-293) compared to Hep-G2 and SH-SY-5Y cells.
  
  
  CONCLUSIONS
  The incorporation of a hydroxyl group in the hydrazide part of a parent molecule which relates to better antioxidant effect in most of the studied systems is associated with higher IC50values in all cytotoxicity experiments and relates to the cytoprotective effect against N-methyl-D-aspartate-induced excitotoxicity in SH-SY5Y human neuronal cells.
authors.affiliation: a Department of Medical Physics and Biophysics, Faculty of Medicine , Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Nadya
authors.identifier: http://orcid.org/0000-0001-7763-9791
authors.initials: N
authors.lastname: Hristova-Avakumova
authors.affiliation: b Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy , Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Krassimira
authors.initials: K
authors.lastname: Yoncheva
authors.affiliation: c Department of Chemistry, Faculty of Pharmacy , Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Boryana
authors.initials: B
authors.lastname: Nikolova-Mladenova
authors.affiliation: a Department of Medical Physics and Biophysics, Faculty of Medicine , Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Trayko
authors.initials: T
authors.lastname: Traykov
authors.affiliation: d Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy , Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Georgi
authors.initials: G
authors.lastname: Momekov
authors.affiliation: a Department of Medical Physics and Biophysics, Faculty of Medicine , Medical University of Sofia , Sofia , Bulgaria.
authors.forename: Vera
authors.identifier: http://orcid.org/0000-0001-7735-5406
authors.initials: V
authors.lastname: Hadjimitova
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D006835:Hydrazones; D017382:Reactive Oxygen Species; D013481:Superoxides; D017665:Hydroxyl Radical
keywords: Hydrazones; antioxidant activity; chemiluminescence; excytotoxicity; polysaccharide particles