title: Design, synthesis, docking studies and biological evaluation of novel chalcone derivatives as potential histone deacetylase inhibitors.
abstract: A group of novel chalcone derivatives comprising hydroxamic acid or 2-aminobenzamide group as zinc binding groups (ZBG) were synthesized. The structure of the prepared compounds was fully characterized by IR, NMR and elemental microanalyses. Most of the tested compounds displayed strong to moderate HDAC inhibitory activity. Some of these compounds showed potent anti-proliferative activity against human HepG2, MCF-7 and HCT-116 cell lines. In particular, compounds 4a and 4b exhibited significant anti-proliferative activity against the three cell lines compared to SAHA as reference drug and displayed promising profile as anti-tumor candidates. The results indicated that these chalcone derivatives could serve as a promising lead compounds for further optimization as antitumor agents.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt.
authors.forename: Mamdouh F A
authors.initials: MFA
authors.lastname: Mohamed
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt.
authors.forename: Montaser Sh A
authors.initials: MSA
authors.lastname: Shaykoon
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt.
authors.forename: Mostafa H
authors.initials: MH
authors.lastname: Abdelrahman
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, 71524 Assiut, Egypt.
authors.forename: Bakheet E M
authors.initials: BEM
authors.lastname: Elsadek
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, 71526 Assiut, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Aboraia
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt. Electronic address: gamal.aborahama@mu.edu.eg.
authors.forename: Gamal El-Din A A
authors.initials: GEAA
authors.lastname: Abuo-Rahma
mesh_terms: D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D002599:Chalcone; D006655:Histone Deacetylases
keywords: Anti-proliferative; Chalcone; Docking; HDAC inhibitors; Histone deacetylase