title: Hydroxamates of para-aminobenzoic acid as selective inhibitors of HDAC8.
abstract: A series of hydroxamates (4a-4l) were prepared from p-aminobenzoic acid to inhibit HDAC8. The idea is to substitute rigid aromatic ring in place of less rigid piperazine ring of hydroxamates reported earlier by our group. It is expected to increase potency retaining the selectivity. Result obtained suggested that the modifications carried out retained the selectivity towards HDAC8 isoform and increasing the potency in very few cases. Increase in potency is also associated with variation in cap aryl region. Two compounds (4f &4l) were found to inhibit HDAC8 at concentrations (IC50) less than 20μM.
authors.affiliation: Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy, Hanamkonda, Warangal 506 001, Andhra Pradesh, India.
authors.forename: Umasankar
authors.initials: U
authors.lastname: Kulandaivelu
authors.affiliation: Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy, Hanamkonda, Warangal 506 001, Andhra Pradesh, India.
authors.forename: Laxmi Manasa
authors.initials: LM
authors.lastname: Chilakamari
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835 215, Jharkhand, India.
authors.forename: Surender Singh
authors.initials: SS
authors.lastname: Jadav
authors.affiliation: Blue Birds College Of Pharmacy, Hanamkonda, Warangal 506 015, Andhra Pradesh, India.
authors.forename: Tadikonda Rama
authors.initials: TR
authors.lastname: Rao
authors.affiliation: Department of Chemistry, Jawaharlal Nehru Technological University Anantapur, College of Engineering, Anantapur 515 002, Andhra Pradesh, India.
authors.forename: K N
authors.initials: KN
authors.lastname: Jayaveera
authors.affiliation: Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy, Hanamkonda, Warangal 506 001, Andhra Pradesh, India.
authors.forename: Boyapati
authors.initials: B
authors.lastname: Shireesha
authors.affiliation: Institute of Pharmaceutical Sciences, Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany.
authors.forename: Alexander-Thomas
authors.initials: AT
authors.lastname: Hauser
authors.affiliation: Institute of Pharmaceutical Sciences, Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Senger
authors.affiliation: Integrated Structural Biology Department, IGBMC, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Marek
authors.affiliation: Integrated Structural Biology Department, IGBMC, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Romier
authors.affiliation: Institute of Pharmaceutical Sciences, Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany. Electronic address: manfred.jung@pharmazie.uni-freiburg.de.
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835 215, Jharkhand, India; Valens Pharma Services, Regus Citi Centre, Level 6, Chennai Citi Centre, 10/11, Dr. Radhakrishnan Salai, Chennai 600 004, Tamil Nadu, India. Electronic address: drvenkatesanj@gmail.com.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
mesh_terms: D010129:4-Aminobenzoic Acid / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases; D010129:4-Aminobenzoic Acid
keywords: HDAC8; Hydroxamates; Inhibitors; Molecular docking; p-Aminobenzoic acid derivatives