title: Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu.
abstract: The synthesis of a series of novel 3,4-cis- and 3,4-trans-substituted carbocyclic nucleoside analogs from protected uracil and thymine is described. The key reaction in the followed synthetic protocols utilized the Mitsunobu reaction to couple 3,4-substituted cyclopentanols to (3)N-benzoyl uracil or (3)N-benzoyl thymine. These molecules were evaluated with regard to their ability to treat diabetic nephropathy. Our results show that two analogs significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro and, more interestingly, exhibited an anti-oxidative effect suggesting that the activity may be mediated through ROS-dependent mechanism.
authors.affiliation: Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon. ae49@aub.edu.lb
authors.forename: Assaad A
authors.initials: AA
authors.lastname: Eid
authors.forename: Ali
authors.initials: A
authors.lastname: Koubeissi
authors.forename: Ribal
authors.initials: R
authors.lastname: Bou-Mjahed
authors.forename: Nadine Al
authors.initials: NA
authors.lastname: Khalil
authors.forename: Manal
authors.initials: M
authors.lastname: Farah
authors.forename: Rita
authors.initials: R
authors.lastname: Maalouf
authors.forename: Niveen
authors.initials: N
authors.lastname: Nasser
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Bouhadir
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000199:Actins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D009705:Nucleosides; D017382:Reactive Oxygen Species; D005947:Glucose