Isolated from the liquid of cashew nut shells, the so-called anacardic acid (5a) is a
non-competitive inhibitor of various HAT enzymes. Depending on the experimental
assay and enzyme purification conditions, its IC 50 values range between 8.5 [77] and
over 1,000 μM [74] for p300/CBP, from 5 [77] to 667.1 μM [74] for PCAF and from
64 [78] to 347.6 μM [74] for Tip60. It is also able to inhibit MOF, with K i and IC 50
values of 64 [79] and 43 μM [78], respectively. One of its most relevant cellular
effects is the repression of NF-κB signalling as a consequence of the inhibition of the
p65 subunit acetylation. Nevertheless, the effects of 5a in various cellular contexts
OH
O
OH
n
9
HO
O
OH
N
OR 2
O
R 1
OH
N
OEt
O
N
OEt
O
R 1
R 2
O
N
H
OEt
O
EtO
O
13
9a SPV106
(LoCAM)
R
O
HO
O
n
9b R = OH, n = 12
9c R = OH, n = 13
9d R = Me, n = 12
9e R = Me, n = 13
8a R 1 = n-Pr, R 2 = H
8b R 1 = Bn, R 2 = H
8c R 1 = Me, R 2 = BnO
8d R 1 = Me, R 2 = PhCOCH 2 O
5c
5a Anacardic acid, n = 14
5b n = 9
7a MC1823
R 1 = n-pentyl, R 2 = H
7b R 1 = Me, R 2 = H
7c R 1 = Me, R 2 = Et
OH O
OH
HO
MeO
OMe
10 Curcumin
O
O
OH O
OH
OH
11a Garcinol
6 MC1626
8e R 1 = Me, R 2 =
O
O
O
O
OH
O
11b Isogarcinol R = H
11c LTK-14
R = Me
R
N
N
O
O
O
OH
11d EML425
O
N
H
HO
O
HO O
COOH
O
NH
HN
N
H
NH 2
NH
O
O
HO
12a NK13650A R = NH-Aspartic acid
12b NK13650B R = OH
R
Fig. 4 HATi from natural sources and related compounds
Histone Acetyltransferase Enzymes: From Biological Implications to Most. . .
107