Identification and optimisation of a series of substituted 5-pyridin-2-yl-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 2, 2007, Pages 363-369

  Price, Steve ^a   Bordogna, Walter ^a   Braganza, Ruth ^a   Bull, Richard J ^a   Dyke, Hazel J ^a   Gardan, Sophie ^a   Gill, Matthew ^a   Harris, Neil V ^a   Heald, Robert A ^a   van den Heuvel, Marco ^a   Lockey, Peter M ^a   Lloyd, Julia ^a   Molina, Aranzazu G ^a   Roach, Alan G ^a   Roussel, Fabien ^a   Sutton, Jonathan M ^a   White, Anne B ^a  

^a Argenta Discovery Ltd   (United Kingdom)

Author keywords

HDAC; Histone deacetylase inhibitors; Hydroxamic acids

Indexed keywords

ADS 100380; ADS 102550; HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID DERIVATIVE; UNCLASSIFIED DRUG; VORINOSTAT;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DEGRADATION; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; MOUSE; NONHUMAN; RAT; SUBSTITUTION REACTION;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; CACO-2 CELLS; CELL LINE, TUMOR; CELL PROLIFERATION; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; HISTONE DEACETYLASES; HUMANS; HYDROXAMIC ACIDS; INDICATORS AND REAGENTS; INJECTIONS, INTRAVENOUS; MICE; MICROSOMES, LIVER; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

RATTUS;

EID: 33846044054     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.10.045     Document Type: Article

References (11)

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9. See the preceding paper:. Price S., Bordogna W., Bull R.J., Clark D.E., Crackett P.H., Dyke H.J., Gill M., Harris N.V., Gorski J., Lloyd J., Lockey P.M., Mullett J., Roach A.G., Roussel F., and White A.B. Bioorg. Med. Chem. Lett. (2006)
10. The HDAC inhibitory activity of compounds was assessed using the commercially available HDAC Fluorescent Activity Assay Kit (Biomol, #AK-500) following the manufacturer instructions, but with minor modifications: the reaction was carried out at 25 °C for 30 min in the presence of 116 μM substrate. Compounds were serially diluted in DMSO and the final concentration of the solvent in the assay was 1%.
11. The anti-proliferative activity of the compounds was tested on a panel of human cancer cell lines. Cells were seeded in 96-well plates at a density of 3000 cell/well and incubated with serially diluted compounds for 72 h. The final DMSO concentration in the assay was 0.1%. The final number of cells per well was assessed using the CyQuant DNA dye (Invitrogen, #C7026) following the manufacturer instructions.