TY - JOUR
T1 - Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors
AU - Cincinelli, Raffaella
AU - Musso, Loana
AU - Giannini, Giuseppe
AU - Zuco, Valentina
AU - De Cesare, Michelandrea
AU - Zunino, Franco
AU - Dallavalle, Sabrina
PY - 2014/5/22
Y1 - 2014/5/22
N2 - To investigate the influence of the adamantyl group on the biological properties of known HDAC inhibitors with a 4-phenylcinnamic skeleton, a series of compounds having the adamantyl moiety in the cap structure were synthesized and compared to the corresponding hydroxamic acids lacking this group. An unexpected finding was the substantial reduction of inhibitory activity toward the tested enzymes, in particular HDAC6, following the introduction of the adamantyl group. In spite of the reduced ability to function as HDAC inhibitors, the compounds containing the adamantyl moiety still retained a good efficacy as antiproliferative and proapoptotic agents. A selected compound (2c; ST3056) of this series exhibited an appreciable antitumor activity against the colon carcinoma xenograft HCT116.
AB - To investigate the influence of the adamantyl group on the biological properties of known HDAC inhibitors with a 4-phenylcinnamic skeleton, a series of compounds having the adamantyl moiety in the cap structure were synthesized and compared to the corresponding hydroxamic acids lacking this group. An unexpected finding was the substantial reduction of inhibitory activity toward the tested enzymes, in particular HDAC6, following the introduction of the adamantyl group. In spite of the reduced ability to function as HDAC inhibitors, the compounds containing the adamantyl moiety still retained a good efficacy as antiproliferative and proapoptotic agents. A selected compound (2c; ST3056) of this series exhibited an appreciable antitumor activity against the colon carcinoma xenograft HCT116.
KW - Adamantyl moiety
KW - Antiproliferative activity
KW - HDAC inhibitors
KW - Hydroxamic acids
UR - http://www.scopus.com/inward/record.url?scp=84921998819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921998819&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2014.04.021
DO - 10.1016/j.ejmech.2014.04.021
M3 - Article
C2 - 24742384
AN - SCOPUS:84921998819
VL - 79
SP - 251
EP - 259
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -