title: Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines.
abstract: We report herein the synthesis of a novel series of carbocyclic acylhydrazone derivatives of uracil, thymine and cytosine from the corresponding nucleic bases and their biological activity to treat diabetic nephropathy. Intriguingly, five derivatives significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. The anti-oxidative effects displayed by these molecules suggest that their activity might involve a ROS-dependent mechanism.
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon. Electronic address: kb05@aub.edu.lb.
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Bouhadir
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Ali
authors.initials: A
authors.lastname: Koubeissi
authors.affiliation: Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Fatima A
authors.initials: FA
authors.lastname: Mohsen
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Mira Diab
authors.initials: MD
authors.lastname: El-Harakeh
authors.affiliation: Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Rouba
authors.initials: R
authors.lastname: Cheaib
authors.affiliation: Medical Engineering Department, Faculty of Medicine, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon.
authors.forename: Joan
authors.initials: J
authors.lastname: Younes
authors.affiliation: Department of Biology, Faculty of Sciences II, Lebanese University, Fanar, Lebanon.
authors.forename: Georges
authors.initials: G
authors.lastname: Azzi
authors.affiliation: Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. Electronic address: ae49@aub.edu.lb.
authors.forename: Assaad A
authors.initials: AA
authors.lastname: Eid
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000199:Actins; D005353:Fibronectins; D009705:Nucleosides; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D005947:Glucose
keywords: Acylhydrazones; Carbocyclic nucleosides; Cytosine; Diabetic nephropathy; Thymine; Uracil