147. Dai W, Zhou J, Jin B et al (2016b) Class III-specific HDAC inhibitor Tenovin-6 induces
apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma. Sci Rep
6:22622. https://doi.org/10.1038/srep22622
148. Hirai S, Endo S, Saito R et al (2014) Antitumor effects of a sirtuin inhibitor, tenovin-6, against
gastric cancer cells via death receptor 5 up-regulation. PLoS One 9(7):e102831. https://doi.
org/10.1371/journal.pone.0102831
149. Ueno T, Endo S, Saito R et al (2013) The sirtuin inhibitor tenovin-6 upregulates death receptor
5 and enhances cytotoxic effects of 5-fluorouracil and oxaliplatin in colon cancer cells. Oncol
Res 21(3):155–164. https://doi.org/10.3727/096504013X13854886566598
150. MacCallum SF, Groves MJ, James J et al (2013) Dysregulation of autophagy in chronic
lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6. Sci Rep 3:1275.
https://doi.org/10.1038/srep01275
151. Yuan H, He M, Cheng F et al (2017) Tenovin-6 inhibits proliferation and survival of diffuse
large B-cell lymphoma cells by blocking autophagy. Oncotarget 8(9):14912–14924. https://
doi.org/10.18632/oncotarget.14741
152. McCarthy AR, Pirrie L, Hollick JJ et al (2012) Synthesis and biological characterisation of
sirtuin inhibitors based on the tenovins. Bioorg Med Chem 20(5):1779–1793. https://doi.org/
10.1016/j.bmc.2012.01.001
153. Pirrie L, McCarthy AR, Major LL et al (2012) Discovery and validation of SIRT2 inhibitors
based on tenovin-6: use of a
1
H-NMR method to assess deacetylase activity. Molecules 17
(10):12206–12224. https://doi.org/10.3390/molecules171012206
154. McCarthy AR, Sachweh MCC, Higgins M et al (2013) Tenovin-D3, a novel small-molecule
inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner.
Mol Cancer Ther 12(4):352–360. https://doi.org/10.1158/1535-7163.MCT-12-0900
155. Disch JS, Evindar G, Chiu CH et al (2013) Discovery of thieno[3,2-d]pyrimidine-6carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3. J Med Chem 56(9):3666–
3679. https://doi.org/10.1021/jm400204k
156. Yoon YK, Ali MA, Wei AC et al (2014) Benzimidazoles as new scaffold of sirtuin inhibitors:
green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer
properties. Eur J Med Chem 83:448–454. https://doi.org/10.1016/j.ejmech.2014.06.060
157. Di Fruscia P, Zacharioudakis E, Liu C et al (2015) The discovery of a highly selective 5,6,7,8tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
SIRT2
inhibitor
that
is
neuroprotective in an in vitro Parkinson’s disease model. ChemMedChem 10(1):69–82.
https://doi.org/10.1002/cmdc.201402431
158. Patel K, Sherrill J, Mrksich M et al (2015) Discovery of SIRT3 inhibitors using SAMDI mass
spectrometry. J Biomol Screen 20(7):842–848. https://doi.org/10.1177/1087057115588512
159. Uciechowska U, Schemies J, Neugebauer RC et al (2008) Thiobarbiturates as sirtuin inhibitors: virtual screening, free-energy calculations, and biological testing. ChemMedChem 3
(12):1965–1976. https://doi.org/10.1002/cmdc.200800104
160. Manjulatha K, Srinivas S, Mulakayala N et al (2012) Ethylenediamine diacetate (EDDA)
mediated synthesis of aurones under ultrasound: their evaluation as inhibitors of SIRT1.
Bioorg Med Chem Lett 22(19):6160–6165. https://doi.org/10.1016/j.bmcl.2012.08.017
161. Zheng YC, Wang LZ, Zhao LJ et al (2016) 1,2,3-Triazole-dithiocarbamate hybrids, a group of
novel cell active SIRT1 inhibitors. Cell Physiol Biochem 38(1):185–193. https://doi.org/10.
1159/000438620
162. Sociali G, Galeno L, Parenti MD et al (2015) Quinazolinedione SIRT6 inhibitors sensitize
cancer cells to chemotherapeutics. Eur J Med Chem 102:530–539. https://doi.org/10.1016/j.
ejmech.2015.08.024
163. Gey C, Kyrylenko S, Hennig L et al (2007) Phloroglucinol derivatives guttiferone G,
aristoforin, and hyperforin: inhibitors of human sirtuins SIRT1 and SIRT2. Angew Chem
Int Ed Engl 46(27):5219–5222. https://doi.org/10.1002/anie.200605207
164. Gutiérrez M, Andrianasolo EH, Shin WK et al (2009) Structural and synthetic investigations of
tanikolide dimer, a SIRT2 selective inhibitor, and tanikolide seco-acid from the Madagascar
90
M. Rahnasto-Rilla et al.
apoptosis, suppresses migration and eliminates cancer stem cells in uveal melanoma. Sci Rep
6:22622. https://doi.org/10.1038/srep22622
148. Hirai S, Endo S, Saito R et al (2014) Antitumor effects of a sirtuin inhibitor, tenovin-6, against
gastric cancer cells via death receptor 5 up-regulation. PLoS One 9(7):e102831. https://doi.
org/10.1371/journal.pone.0102831
149. Ueno T, Endo S, Saito R et al (2013) The sirtuin inhibitor tenovin-6 upregulates death receptor
5 and enhances cytotoxic effects of 5-fluorouracil and oxaliplatin in colon cancer cells. Oncol
Res 21(3):155–164. https://doi.org/10.3727/096504013X13854886566598
150. MacCallum SF, Groves MJ, James J et al (2013) Dysregulation of autophagy in chronic
lymphocytic leukemia with the small-molecule Sirtuin inhibitor Tenovin-6. Sci Rep 3:1275.
https://doi.org/10.1038/srep01275
151. Yuan H, He M, Cheng F et al (2017) Tenovin-6 inhibits proliferation and survival of diffuse
large B-cell lymphoma cells by blocking autophagy. Oncotarget 8(9):14912–14924. https://
doi.org/10.18632/oncotarget.14741
152. McCarthy AR, Pirrie L, Hollick JJ et al (2012) Synthesis and biological characterisation of
sirtuin inhibitors based on the tenovins. Bioorg Med Chem 20(5):1779–1793. https://doi.org/
10.1016/j.bmc.2012.01.001
153. Pirrie L, McCarthy AR, Major LL et al (2012) Discovery and validation of SIRT2 inhibitors
based on tenovin-6: use of a
1
H-NMR method to assess deacetylase activity. Molecules 17
(10):12206–12224. https://doi.org/10.3390/molecules171012206
154. McCarthy AR, Sachweh MCC, Higgins M et al (2013) Tenovin-D3, a novel small-molecule
inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner.
Mol Cancer Ther 12(4):352–360. https://doi.org/10.1158/1535-7163.MCT-12-0900
155. Disch JS, Evindar G, Chiu CH et al (2013) Discovery of thieno[3,2-d]pyrimidine-6carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3. J Med Chem 56(9):3666–
3679. https://doi.org/10.1021/jm400204k
156. Yoon YK, Ali MA, Wei AC et al (2014) Benzimidazoles as new scaffold of sirtuin inhibitors:
green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer
properties. Eur J Med Chem 83:448–454. https://doi.org/10.1016/j.ejmech.2014.06.060
157. Di Fruscia P, Zacharioudakis E, Liu C et al (2015) The discovery of a highly selective 5,6,7,8tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
SIRT2
inhibitor
that
is
neuroprotective in an in vitro Parkinson’s disease model. ChemMedChem 10(1):69–82.
https://doi.org/10.1002/cmdc.201402431
158. Patel K, Sherrill J, Mrksich M et al (2015) Discovery of SIRT3 inhibitors using SAMDI mass
spectrometry. J Biomol Screen 20(7):842–848. https://doi.org/10.1177/1087057115588512
159. Uciechowska U, Schemies J, Neugebauer RC et al (2008) Thiobarbiturates as sirtuin inhibitors: virtual screening, free-energy calculations, and biological testing. ChemMedChem 3
(12):1965–1976. https://doi.org/10.1002/cmdc.200800104
160. Manjulatha K, Srinivas S, Mulakayala N et al (2012) Ethylenediamine diacetate (EDDA)
mediated synthesis of aurones under ultrasound: their evaluation as inhibitors of SIRT1.
Bioorg Med Chem Lett 22(19):6160–6165. https://doi.org/10.1016/j.bmcl.2012.08.017
161. Zheng YC, Wang LZ, Zhao LJ et al (2016) 1,2,3-Triazole-dithiocarbamate hybrids, a group of
novel cell active SIRT1 inhibitors. Cell Physiol Biochem 38(1):185–193. https://doi.org/10.
1159/000438620
162. Sociali G, Galeno L, Parenti MD et al (2015) Quinazolinedione SIRT6 inhibitors sensitize
cancer cells to chemotherapeutics. Eur J Med Chem 102:530–539. https://doi.org/10.1016/j.
ejmech.2015.08.024
163. Gey C, Kyrylenko S, Hennig L et al (2007) Phloroglucinol derivatives guttiferone G,
aristoforin, and hyperforin: inhibitors of human sirtuins SIRT1 and SIRT2. Angew Chem
Int Ed Engl 46(27):5219–5222. https://doi.org/10.1002/anie.200605207
164. Gutiérrez M, Andrianasolo EH, Shin WK et al (2009) Structural and synthetic investigations of
tanikolide dimer, a SIRT2 selective inhibitor, and tanikolide seco-acid from the Madagascar
90
M. Rahnasto-Rilla et al.