title: Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.
abstract: Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself.
authors.affiliation: Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt.
authors.forename: Roba
authors.initials: R
authors.lastname: Talaat
authors.affiliation: Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt.
authors.forename: Waheba
authors.initials: W
authors.lastname: El-Sayed
authors.affiliation: Chemistry Department, Faculty of Science, Menoufiya University, Shebin El-Koam, Egypt.
authors.forename: Hussein S
authors.initials: HS
authors.lastname: Agwa
authors.affiliation: Cancer Biology Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki 12622, Cairo, Egypt.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
authors.affiliation: Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt.
authors.forename: Shaden
authors.initials: S
authors.lastname: Moawia
authors.affiliation: Chemistry Department, Faculty of Science, Menoufiya University, Shebin El-Koam, Egypt. Electronic address: magdyzahran53@gmail.com.
authors.forename: Magdy A H
authors.initials: MA
authors.lastname: Zahran
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D017665:Hydroxyl Radical / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D013792:Thalidomide
keywords: Anti-inflammatory; Hydroxyl (OH()) radical; Prooxidant activity; Thalidomide analogs