(58) outlined the synthesis, characterization, and biological evaluation of suberoylanilide hydroxamic acid (SAHA)-based derivatives with greater binding towards HDAC8
than the SAHA.
CdLS is a rare multisystem genetic disease mainly caused by the mutations of genes code for cohesion system including SMC1A , SMC3 , RAD21 , NIPBL , and HDAC8
. Cohesion plays a key role in the maintenance of genomic stability, as it is involved in the regulation of gene expressing, DNA repair, sister chromatid cohesion, chromatin remodeling, and long-range gene interactions.
Bid et al., "HDAC8
, a potential therapeutic target for the treatment of malignant peripheral nerve sheath tumors (MPNST)," PLoS One, vol.
Hsiao, "The novel HDAC8
inhibitor WK2-16 attenuates lipopolysaccharide-activated matrix metalloproteinase-9 expression in human monocytic cells and improves hypercytokinemia in vivo," International Journal of Molecular Sciences, vol.
The primers used were HDAC1: forward 5'-AGACAGCTGTGGCCCTGGA TAC-3' and reverse 5'-CGGCAGCATTCTAAGGTTCTC AA-3', HDAC2: forward 5'-TGCAGTTGCCCTTGATTGT GA-3' and reverse 5'-ATCTGGACACCAGGTGCATGAG3', HDAC3: forward 5'-AGAGTGGCCGCTACTACTGTC TGAA-3' and reverse 5'-TGGGTTGGTAGAAGTCCAC TACCTG-3', HDAC8
: forward 5'-TGACGGAATGTGCA AAGTAGCAA-3' and reverse 5'-TCAAATTTCCGTCGCA ATCGTA-3', and GAPDH: forward 5'-GTGAACCATGA GAAGTATGACAAC-3' and reverse 5'-CATGAGTCCTT CCACGATACC-3'.
Mutations in the NIPBL, SMC1A, SMC3, RAD21, and HDAC8
genes have been identified to cause CdLS (4).
HDACs can be divided into four distinct families, of particular interest are class I (HDAC1, HDAC2, HDAC5, and HDAC8
) and class II (HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10) HDACs .
In accordance with their structural diversity, HDACs are divided into four subtypes: Class I (HDAC1, HDAC2, HDAC3, and HDAC8
), Class II consisting of IIa (HDAC4, HDAC5, HDAC7, and HDAC9) and IIb (HDAC6 and HDAC10), Class III (a family of sirtuins), and Class IV (HDAC11) .
While direct association with HDACs 1-3 is observed with all MTG family members, the ability to interact with HDAC6 and HDAC8
is unique to MTG16 .
Another study in order to synthesize novel 6-(4-(4- aminophenylsulfonyl)phenylamino)-5H- benzo[a]phenoxazin-5-one derivatives has been published in addition to their molecular docking study with histone deacetylase (HDAC8
) and cytotoxicity against cervical cancer cell line.
Pharmacophore model on histone deacetylase (HDAC8
) with known hydroxamic acids has shown four pharmacophore features: one hydrogen acceptor, two hydrogen donors, and one hydrophobic group .
HDAC6 and HDAC8
enzyme activities contribute to cardiac hypertrophy and fibrosis in the heart obtained from chronic hypertensive rats .