title: Appraisal of GABA and PABA as linker: design and synthesis of novel benzamide based histone deacetylase inhibitors.
abstract: 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.
authors.affiliation: Medicinal Chemistry Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur 495 009, CG, India. harishdops@yahoo.co.in
authors.forename: Harish
authors.initials: H
authors.lastname: Rajak
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
authors.forename: Poonam
authors.initials: P
authors.lastname: Parmar
authors.forename: Bhupendra Singh
authors.initials: BS
authors.lastname: Thakur
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Veerasamy
authors.forename: Prabodh Chander
authors.initials: PC
authors.lastname: Sharma
authors.forename: Ajay Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Gupta
authors.forename: Jawahar Singh
authors.initials: JS
authors.lastname: Dangi
mesh_terms: D010129:4-Aminobenzoic Acid / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D005680:gamma-Aminobutyric Acid / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D005680:gamma-Aminobutyric Acid; C037689:benzamide; D006655:Histone Deacetylases; D010129:4-Aminobenzoic Acid