Exploring the connection unit in the HDAC inhibitor pharmacophore model: novel
uracil-based hydroxamates.

Antonello Mai; Silvio Massa; Dante Rotili; Riccardo Pezzi; Patrizia Bottoni; Roberto Scatena; Joachim Meraner; Gerald Brosch

Exploring the connection unit in the HDAC inhibitor pharmacophore model: novel uracil-based hydroxamates.

Antonello Mai, Silvio Massa, Dante Rotili, Riccardo Pezzi, Patrizia Bottoni, Roberto Scatena, Joachim Meraner, Gerald Brosch

Università Cattolica del Sacro Cuore

Risultato della ricerca: Contributo in rivista › Articolo in rivista

39 Citazioni (Scopus)

Abstract

Starting from the pharmacophore model for HDAC inhibitor design, a novel series of hydroxamates bearing a uracil moiety as connecting unit (CU) has been prepared and tested. Almost all compounds exhibited HDAC inhibiting activity at low nanomolar concentrations, the N-hydroxy-6-(3,4-dihydro-4-oxo-6-benzyl- and -6-phenyl-2-pyrimidinylthio)hexanamides 1d and 1l being more potent than SAHA in enzymatic assays. Such compounds also caused hyperacetylation in NIH3T3 cell core histones and were endowed with interesting antiproliferative and cytodifferentiating effects in human leukemia (HL-60) cells.

Lingua originale	English
pagine (da-a)	4656-4661
Numero di pagine	6
Rivista	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Stato di pubblicazione	Pubblicato - 2005

Keywords

cancer
cell differentiation
drug

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abstract = "Starting from the pharmacophore model for HDAC inhibitor design, a novel series of hydroxamates bearing a uracil moiety as connecting unit (CU) has been prepared and tested. Almost all compounds exhibited HDAC inhibiting activity at low nanomolar concentrations, the N-hydroxy-6-(3,4-dihydro-4-oxo-6-benzyl- and -6-phenyl-2-pyrimidinylthio)hexanamides 1d and 1l being more potent than SAHA in enzymatic assays. Such compounds also caused hyperacetylation in NIH3T3 cell core histones and were endowed with interesting antiproliferative and cytodifferentiating effects in human leukemia (HL-60) cells.",

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T1 - Exploring the connection unit in the HDAC inhibitor pharmacophore model: novel uracil-based hydroxamates.

AU - Mai, Antonello

AU - Massa, Silvio

AU - Rotili, Dante

AU - Pezzi, Riccardo

AU - Bottoni, Patrizia

AU - Scatena, Roberto

AU - Meraner, Joachim

AU - Brosch, Gerald

PY - 2005

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N2 - Starting from the pharmacophore model for HDAC inhibitor design, a novel series of hydroxamates bearing a uracil moiety as connecting unit (CU) has been prepared and tested. Almost all compounds exhibited HDAC inhibiting activity at low nanomolar concentrations, the N-hydroxy-6-(3,4-dihydro-4-oxo-6-benzyl- and -6-phenyl-2-pyrimidinylthio)hexanamides 1d and 1l being more potent than SAHA in enzymatic assays. Such compounds also caused hyperacetylation in NIH3T3 cell core histones and were endowed with interesting antiproliferative and cytodifferentiating effects in human leukemia (HL-60) cells.

AB - Starting from the pharmacophore model for HDAC inhibitor design, a novel series of hydroxamates bearing a uracil moiety as connecting unit (CU) has been prepared and tested. Almost all compounds exhibited HDAC inhibiting activity at low nanomolar concentrations, the N-hydroxy-6-(3,4-dihydro-4-oxo-6-benzyl- and -6-phenyl-2-pyrimidinylthio)hexanamides 1d and 1l being more potent than SAHA in enzymatic assays. Such compounds also caused hyperacetylation in NIH3T3 cell core histones and were endowed with interesting antiproliferative and cytodifferentiating effects in human leukemia (HL-60) cells.

KW - cancer

KW - cell differentiation

KW - drug

KW - cancer

KW - cell differentiation

KW - drug

UR - http://hdl.handle.net/10807/8904

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JO - BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

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