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93. Neugebauer RC, Uchiechowska U, Meier R et al (2008) Structure-activity studies on
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94. Liu FC, Day YJ, Liou JT et al (2012a) Splitomicin inhibits MLP-induced superoxide anion
production in human neutrophils by activate cAMP/PKA signaling inhibition of ERK pathway. Eur J Pharmacol 688(1–3):68–75. https://doi.org/10.1016/j.ejphar.2012.05.006
95. Heltweg B, Gatbonton T, Schuler AD et al (2006) Antitumor activity of a small-molecule
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https://doi.org/10.1158/0008-5472.CAN-05-3617
96. Figuera-Losada M, Stathis M, Dorskind JM (2015) Cambinol, a novel inhibitor of neutral
sphingomyelinase 2 shows neuroprotective properties. PLoS One 10(5):e0124481. https://doi.
org/10.1371/journal.pone.0124481
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inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. J
Biol Chem 276(42):38837–38843. https://doi.org/10.1074/jbc.M106779200
79. Mai A, Massa S, Lavu S et al (2005) Design, synthesis, and biological evaluation of
sirtinol analogues as class III histone/protein deacetylase (sirtuin) inhibitors. J Med Chem
48(24):7789–7795. https://doi.org/10.1021/jm050100l
80. Maurer B, Rumpf T, Scharfe M et al (2012) Inhibitors of the NAD(+)-dependent protein
desuccinylase and demalonylase sirt5. ACS Med Chem Lett 3(12):1050–1053. https://doi.org/
10.1021/ml3002709
81. Ota H, Tokunaga E, Chang K et al (2006) Sirt1 inhibitor, Sirtinol, induces senescence-like
growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene
25(2):176–185. https://doi.org/10.1038/sj.onc.1209049
82. Peck B, Chen CY, Ho KK et al (2010) SIRT inhibitors induce cell death and p53 acetylation
through targeting both SIRT1 and SIRT2. Mol Cancer Ther 9(4):844–855. https://doi.org/10.
1158/1535-7163.MCT-09-0971
83. Kalle AM, Mallika A, Badiger J et al (2010) Inhibition of SIRT1 by a small molecule induces
apoptosis in breast cancer cells. Biochem Biophys Res Commun 401(1):13–19. https://doi.org/
10.1016/j.bbrc.2010.08.118
84. Dastjerdi MN, Salahshoor MR, Mardani M et al (2013) The apoptotic effects of sirtuin1
inhibitor on the MCF-7 and MRC-5 cell lines. Res Pharm Sci 8(2):79–89
85. Lara E, Mai A, Calvanese V et al (2009) Salermide, a Sirtuin inhibitor with a strong cancerspecific proapoptotic effect. Oncogene 28(6):781–791. https://doi.org/10.1038/onc.2008.436
86. Liu G, Su L, Hao X et al (2012b) Salermide up-regulates death receptor 5 expression through
the ATF4-ATF3-CHOP axis and leads to apoptosis in human cancer cells. J Cell Mol Med
16(7):1618–1628. https://doi.org/10.1111/j.1582-4934.2011.01401.x
87. Rotili D, Tarantino D, Nebbioso A et al (2012b) Discovery of salermide-related sirtuin
inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer
stem cells. J Med Chem 55(24):10937–10947. https://doi.org/10.1021/jm3011614
88. Bedalov A, Gatbonton T, Irvine WP et al (2001) Identification of a small molecule inhibitor
of Sir2p. Proc Natl Acad Sci U S A 98(26):15113–15118. https://doi.org/10.1073/pnas.
261574398
89. Hirao M, Posakony J, Nelson M et al (2003) Identification of selective inhibitors of NAD+dependent deacetylases using phenotypic screens in yeast. J Biol Chem 278
(52):52773–52782. https://doi.org/10.1074/jbc.M308966200
90. Pagans S, Pedal A, North BJ et al (2005) SIRT1 regulates HIV transcription via Tat
deacetylation. PLoS Biol 3(2):e41. https://doi.org/10.1371/journal.pbio.0030041
91. Posakony J, Hirao M, Stevens S et al (2004) Inhibitors of Sir2: evaluation of splitomicin
analogues. J Med Chem 47(10):2635–2644. https://doi.org/10.1021/jm030473r
92. Freitag M, Schemies J, Larsen T et al (2011) Synthesis and biological activity of splitomicin
analogs targeted at human NAD(+)-dependent histone deacetylases (sirtuins). Bioorg Med
Chem 19(12):3669–3677. https://doi.org/10.1016/j.bmc.2011.01.026
93. Neugebauer RC, Uchiechowska U, Meier R et al (2008) Structure-activity studies on
splitomicin derivatives as sirtuin inhibitors and computational prediction of binding mode.
J Med Chem 51(5):1203–1213. https://doi.org/10.1021/jm700972e
94. Liu FC, Day YJ, Liou JT et al (2012a) Splitomicin inhibits MLP-induced superoxide anion
production in human neutrophils by activate cAMP/PKA signaling inhibition of ERK pathway. Eur J Pharmacol 688(1–3):68–75. https://doi.org/10.1016/j.ejphar.2012.05.006
95. Heltweg B, Gatbonton T, Schuler AD et al (2006) Antitumor activity of a small-molecule
inhibitor of human silent information regulator 2 enzymes. Cancer Res 66(8):4368–4377.
https://doi.org/10.1158/0008-5472.CAN-05-3617
96. Figuera-Losada M, Stathis M, Dorskind JM (2015) Cambinol, a novel inhibitor of neutral
sphingomyelinase 2 shows neuroprotective properties. PLoS One 10(5):e0124481. https://doi.
org/10.1371/journal.pone.0124481
86
M. Rahnasto-Rilla et al.