Abstract
Mycophenolic acid (MPA, 1), an inhibitor of IMP-dehydrogenase (IMPDH) and a latent PPARγ agonist, is used as an effective immunosuppressant for clinical transplantation and recently entered clinical trials in advanced multiple myeloma patients. On the other hand, suberoylanilide hydroxamic acid (SAHA), a non-specific histone deacetylase (HDAC) inhibitor, has been approved for treating cutaneous T-cell lymphoma. MPA seemed to bear a cap, a linker, and a weak metal-binding site as a latent inhibitor of HDAC. Therefore, the hydroxamic acid derivatives of mycophenolic acid having an effective metal-binding site, mycophenolic hydroxamic acid (MPHA, 2), 7-O-acetyl mycophenolic acid (7-O-Ac MPHA, 3), and 7-O-lauroyl mycophenolic hydroxamic acid (7-O-L MPHA, 4) were designed and synthesized. All these compounds inhibited histone deacetylase with IC50 values of 1, 0.9 and 0.5 μM, and cell proliferation at concentrations of 2, 1.5 and 1 μM, respectively.
| Original language | English |
|---|---|
| Pages (from-to) | 2623-2631 |
| Number of pages | 9 |
| Journal | Bioscience, Biotechnology and Biochemistry |
| Volume | 72 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2008 Nov 5 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Analytical Chemistry
- Biochemistry
- Applied Microbiology and Biotechnology
- Molecular Biology
- Organic Chemistry
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Hydroxamic acid derivatives of mycophenolic acid inhibit histone deacetylase at the cellular level. / Batovska, Daniela I.; Kim, Dong Hoon; Mitsuhashi, Shinya; Cho, Yoon Sun; Kwon, Ho Jeong; Ubukata, Makoto.
In: Bioscience, Biotechnology and Biochemistry, Vol. 72, No. 10, 05.11.2008, p. 2623-2631.Research output: Contribution to journal › Article
TY - JOUR
T1 - Hydroxamic acid derivatives of mycophenolic acid inhibit histone deacetylase at the cellular level
AU - Batovska, Daniela I.
AU - Kim, Dong Hoon
AU - Mitsuhashi, Shinya
AU - Cho, Yoon Sun
AU - Kwon, Ho Jeong
AU - Ubukata, Makoto
PY - 2008/11/5
Y1 - 2008/11/5
N2 - Mycophenolic acid (MPA, 1), an inhibitor of IMP-dehydrogenase (IMPDH) and a latent PPARγ agonist, is used as an effective immunosuppressant for clinical transplantation and recently entered clinical trials in advanced multiple myeloma patients. On the other hand, suberoylanilide hydroxamic acid (SAHA), a non-specific histone deacetylase (HDAC) inhibitor, has been approved for treating cutaneous T-cell lymphoma. MPA seemed to bear a cap, a linker, and a weak metal-binding site as a latent inhibitor of HDAC. Therefore, the hydroxamic acid derivatives of mycophenolic acid having an effective metal-binding site, mycophenolic hydroxamic acid (MPHA, 2), 7-O-acetyl mycophenolic acid (7-O-Ac MPHA, 3), and 7-O-lauroyl mycophenolic hydroxamic acid (7-O-L MPHA, 4) were designed and synthesized. All these compounds inhibited histone deacetylase with IC50 values of 1, 0.9 and 0.5 μM, and cell proliferation at concentrations of 2, 1.5 and 1 μM, respectively.
AB - Mycophenolic acid (MPA, 1), an inhibitor of IMP-dehydrogenase (IMPDH) and a latent PPARγ agonist, is used as an effective immunosuppressant for clinical transplantation and recently entered clinical trials in advanced multiple myeloma patients. On the other hand, suberoylanilide hydroxamic acid (SAHA), a non-specific histone deacetylase (HDAC) inhibitor, has been approved for treating cutaneous T-cell lymphoma. MPA seemed to bear a cap, a linker, and a weak metal-binding site as a latent inhibitor of HDAC. Therefore, the hydroxamic acid derivatives of mycophenolic acid having an effective metal-binding site, mycophenolic hydroxamic acid (MPHA, 2), 7-O-acetyl mycophenolic acid (7-O-Ac MPHA, 3), and 7-O-lauroyl mycophenolic hydroxamic acid (7-O-L MPHA, 4) were designed and synthesized. All these compounds inhibited histone deacetylase with IC50 values of 1, 0.9 and 0.5 μM, and cell proliferation at concentrations of 2, 1.5 and 1 μM, respectively.
UR - http://www.scopus.com/inward/record.url?scp=55049101683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55049101683&partnerID=8YFLogxK
U2 - 10.1271/bbb.80303
DO - 10.1271/bbb.80303
M3 - Article
C2 - 18838793
AN - SCOPUS:55049101683
VL - 72
SP - 2623
EP - 2631
JO - Bioscience, Biotechnology and Biochemistry
JF - Bioscience, Biotechnology and Biochemistry
SN - 0916-8451
IS - 10
ER -