Appraisal of GABA and PABA as linker: Design and synthesis of novel benzamide based histone deacetylase inhibitors

• DOI: 10.1016/j.ejmech.2012.03.058
• Publication Date: 2012-04-11T18:24:00Z
• Authors: Harish Rajak; Pramod Kumar; Poonam Parmar; Bhupendra Singh T...; Ravichandran Veer...; Prabodh Chander S...; Ajay Kumar Sharma; Arun Kumar Gupta; Jawahar Singh Dangi
• Keywords: 0301 basic medicine; Antineoplastic Agents; Chemistry Techniques, Synthetic; HCT116 Cells; Histone Deacetylases; 3. Good health; Histone Deacetylase Inhibitors; Mice; 03 medical and health sciences; Drug Design; Benzamides; Animals; Humans; 4-Aminobenzoic Acid; gamma-Aminobutyric Acid; Cell Proliferation

Histone deacetylase inhibitors have been actively explored as a new generation of chemotherapeutics for cancers, generally known as epigenetic therapeutics. Two novel series of N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}-butyramide and N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}benzamide were designed and synthesized as novel histone deacetylase inhibitors. The anticancer potential of the compounds were determined in-vitro using MTT assay against HCT-116 and U251 (glioma) cell lines and histone deacetylase inhibitory assay. The synthesized compounds were investigated for anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. The efforts were also made to ascertain structure-activity relationships among test compounds. The results of the present studying represents appraisal of γ-aminobutyric acid (GABA) and para-aminobenzoic acid (PABA) as linker moiety for development of newer benzamide based histone deacetylase inhibitor.