Identification of a potent and stable antiproliferative agent by the prodrug formation of a thiolate histone deacetylase inhibitor

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 6, 2007, Pages 1558-1561

  Suzuki, Takayoshi ^a   Hisakawa, Shinya ^a   Itoh, Yukihiro ^a   Maruyama, Sakiko ^b   Kurotaki, Mineko ^b   Nakagawa, Hidehiko ^a   Miyata, Naoki ^a  

^a NAGOYA CITY UNIVERSITY   (Japan)

^b Drug Research Department   (Japan)

Author keywords

Antiproliferative agent; Histone deacetylase inhibitor; Prodrug

Indexed keywords

HISTONE DEACETYLASE INHIBITOR; NCH 31; NCH 51; PRODRUG; THIOL DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BENZYLATION; CANCER CELL CULTURE; CELL PROLIFERATION; CHIRALITY; COLUMN CHROMATOGRAPHY; CONTROLLED STUDY; DRUG POTENCY; DRUG STABILITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; POLYMERIZATION; STEREOISOMERISM; WESTERN BLOTTING;

ANTINEOPLASTIC AGENTS; BLOTTING, WESTERN; CELL LINE, TUMOR; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HISTONE DEACETYLASE INHIBITORS; HUMANS; PRODRUGS; THIAZOLES;

EID: 33847213896     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.12.117     Document Type: Article

References (18)

1. Suzuki T., and Miyata N. Curr. Med. Chem. 13 (2006) 935
2. Biel M., Wascholowski V., and Giannis A. Angew. Chem. Int. Ed. 44 (2005) 3186
3. Taunton J., Hassig C.A., and Schreiber S.L. Science 272 (1996) 408
4. Fraga M.F., Ballestar E., Villar-Garea A., Boix-Chornet M., Espada J., Schotta G., Bonaldi T., Haydon C., Ropero S., Petrie K., Iyer N.G., Perez-Rosado A., Calvo E., Lopez J.A., Cano A., Calasanz M.J., Colomer D., Piris M.A., Ahn N., Imhof A., Caldas C., Jenuwein T., and Esteller M. Nat. Genet. 37 (2005) 391
5. Seligson D.B., Horvath S., Shi T., Yu H., Tze S., Grunstein M., and Kurdistani S.K. Nature 435 (2005) 1262
6. Sambucetti L.C., Fischer D.D., Zabludoff S., Kwon P.O., Chamberlin H., Trogani N., Xu H., and Cohen D. J. Biol. Chem. 274 (1999) 34940
7. Bali P., Pranpat M., Bradner J., Balasis M., Fiskus W., Guo F., Rocha K., Kumaraswamy S., Boyapalle S., Atadja P., Seto E., and Bhalla K. J. Biol. Chem. 280 (2005) 26729
8. Hideshima T., Bradner J.E., Wong J., Chauhan D., Richardson P., Schreiber S.L., and Anderson K.C. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 8567
9. Yoshida M., Horinouchi S., and Beppu T. BioEssays 17 (1995) 423
10. Richon V.M., Emiliani S., Verdin E., Webb Y., Breslow R., Rifkind R.A., and Marks P.A. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 3003
11. Suzuki T., Kouketsu A., Matsuura A., Kohara A., Ninomiya S., Kohda K., and Miyata N. Bioorg. Med. Chem. Lett. 14 (2004) 3313
12. Suzuki T., Nagano Y., Kouketsu A., Matsuura A., Maruyama S., Kurotaki M., Nakagawa H., and Miyata N. J. Med. Chem. 48 (2005) 1019
13. 2 for 48 h. The medium was removed and replaced with 200 μL of 0.5 mg/mL of methylene blue in RPMI-1640 medium, and cells were incubated at room temperature for 30 min. Supernatants were removed from the wells, and methylene blue dye was dissolved in 100 μL/well of 3% aqueous HCl. Absorbance was determined on a microplate reader (Bio-Rad) at 660 nm.
14. Davies S.G., and Sanganee H.J. Tetrahedron: Asymmetry 6 (1995) 671
15. Analytical conditions of chiral column chromatography; column: CHIRALCEL OA (Daicel Chemical Industries), eluent: n-hexane/isopropanol = 19:1, flow rate: 1 mL/min; retention time: 27.4 min ((R)-2), 29.3 min ((S)-2).
16. The inhibitory activities of test compounds against partially purified HDAC1 were assayed according to a method reported in the literature:. Furumai R., Komatsu Y., Nishino N., Khochbin S., Yoshida M., and Horinouchi S. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 87
17. 5) were treated for 8 h with 5 μM of SAHA or compound 2 in 10% FBS-supplemented McCoy's 5A medium and then collected and extracted with SDS buffer. Protein concentrations of the lysates were determined using a Bradford protein assay kit (Bio-Rad Laboratories); equivalent amounts of proteins from each lysate were resolved in 15% SDS-polyacrylamide gel and then transferred onto nitrocellulose membranes (Bio-Rad Laboratories). After blocking for 30 min with Tris-buffered saline (TBS) containing 3% skim milk, the transblotted membrane was incubated overnight at 4 °C with hyperacetylated histone H4 antibody (Upstate Biotechnology) (1:4000 dilution) in TBS containing 3% skim milk. After probing with the primary antibody, the membrane was washed twice with water, then incubated with goat anti-rabbit IgG-horseradish peroxidase conjugates (diluted 1:5000) for 2 h at room temperature, and further washed twice with water. The immunoblots were visualized by enhanced chemiluminescence.
18. NCH-51 and compound 2 (100 μM) were incubated at 37 °C in human plasma. The percentage of the parent compound remaining (%R) was determined by HPLC.