Design and Synthesis of Novel 2, 5-Disubstituted-1, 3, 4-Thiadiazoles and Oxadiazoles as Histone Deacetylase Inhibitors

Author(s)

Somani, R.R., Jain, M.H., Vora, P.K., Patil, P.M., Parab, S.S.

Author's Affiliation

Abstract

Histone deacetylases (HDACs) have been widely recognized as promising targets for cancer treatment. Accumulated clinical studies have demonstrated that HDACs inhibitors show great potential for the treatment of cancer. SAHA (Vorinostat, trade name Zolinza^®) and Trichostatin A (TSA) where approved by the FDA in 2006 for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma. As a continuity of our ongoing effort to identify novel small molecules targeting these important enzymes, we designed and synthesized two series of azole based 2, 5-Disubstituted-1, 3, 4-Thiadiazoles (5a-e) and 2, 5-Disubstituted 1, 3, 4-Oxadiazoles (5f-j) as histone deacetylase inhibitors as analogues of SAHA. Ligand-based virtual screening methods were employed to identify novel HDAC inhibitors. Docking study all compounds revealed that these compounds bound to HDAC-2 i.e. 3MAX PDB CODE with higher affinities compared to SAHA and Trichostatin A. These findings should encourage further elaboration with the azole moiety to produce more potent HDAC inhibitors with potential anti-cancer activity. They were tested for anti-cancer, anti-bacterial and anti-fungal activity. Synthesized compounds possessed good anti-bacterial and anti-fungal activity as compared to standard drug.

Keywords

Anti-cancer, 2, 5-Disubstituted 1, 3, 4-Oxadiazoles,   2, 5-Disubstituted-1, 3, 4-Thiadiazoles, Histone deacetylase inhibitor, SAHA

Cite This Article

Somani, R.R., Jain, M.H., Vora, P.K., Patil, P.M., Parab, S.S. (2016). Design and Synthesis of Novel 2, 5-Disubstituted-1, 3, 4-Thiadiazoles and Oxadiazoles as Histone Deacetylase Inhibitors, International Journal for Pharmaceutical Research Scholars (IJPRS), 5(2), 271-285.