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

Kamal H Bouhadir; Ali Koubeissi; Fatima A Mohsen; Mira Diab El-Harakeh; Rouba Cheaib; Joan Younes; Georges Azzi; Assaad A Eid

doi:10.1016/j.bmcl.2015.12.042

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

Bioorg Med Chem Lett. 2016 Feb 1;26(3):1020-1024. doi: 10.1016/j.bmcl.2015.12.042. Epub 2015 Dec 12.

Authors

Kamal H Bouhadir¹, Ali Koubeissi², Fatima A Mohsen³, Mira Diab El-Harakeh², Rouba Cheaib², Joan Younes⁴, Georges Azzi⁵, Assaad A Eid⁶

Affiliations

¹ Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon. Electronic address: [email protected].
² Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
³ Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
⁴ Medical Engineering Department, Faculty of Medicine, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon.
⁵ Department of Biology, Faculty of Sciences II, Lebanese University, Fanar, Lebanon.
⁶ Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. Electronic address: [email protected].

PMID: 26733477
DOI: 10.1016/j.bmcl.2015.12.042

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.

Keywords: Acylhydrazones; Carbocyclic nucleosides; Cytosine; Diabetic nephropathy; Thymine; Uracil.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism
Animals
Cell Proliferation / drug effects
Cells, Cultured
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / pathology
Fibronectins / metabolism
Glucose / pharmacology
Mesangial Cells / cytology
Mesangial Cells / drug effects
Mesangial Cells / metabolism
Nucleosides / chemical synthesis
Nucleosides / chemistry*
Nucleosides / pharmacology
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Rats
Reactive Oxygen Species / metabolism

Substances

Actins
Fibronectins
Nucleosides
Pyrimidines
Reactive Oxygen Species
Glucose