title: 2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors.
abstract: The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid 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: Avantika
authors.initials: A
authors.lastname: Agarawal
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: Murli Dhar
authors.initials: MD
authors.lastname: Kharya
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D049109:Cell Proliferation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000737:chemistry; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D010069:Oxadiazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013830:Thiadiazoles / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010069:Oxadiazoles; D013830:Thiadiazoles; D015032:Zinc