Phenylpyrrole-based HDAC inhibitors: Synthesis, molecular modeling and biological studies

Future Medicinal Chemistry

Volumn 8, Issue 13, 2016, Pages 1573-1587

  Brindisi, Margherita ^a   Cavella, Caterina ^a   Brogi, Simone ^a   Nebbioso, Angela ^b,c   Senger, Johanna ^d   Maramai, Samuele ^a   Ciotta, Alfonso ^b,c   Iside, Concetta ^b,c   Butini, Stefania ^a   Lamponi, Stefania ^a   Novellino, Ettore ^e   Altucci, Lucia ^b,c   Jung, Manfred ^d   Campiani, Giuseppe ^a   Gemma, Sandra ^a  

^a UNIVERSITY OF SIENA   (Italy)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

^c INSTITUTE OF GENETICS AND BIOPHYSICS ADRIANO BUZZATI TRAVERSO   (Italy)

^d UNIVERSITY OF FREIBURG   (Germany)

^e UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

antitumor agents; bioinformatics; drug design; enzyme inhibitors; epigenetics; HDAC

Indexed keywords

ALPHA TUBULIN; CYTOTOXIC AGENT; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; HYDROXAMIC ACID DERIVATIVE; PYRROLE DERIVATIVE; HDAC1 PROTEIN, HUMAN; HDAC6 PROTEIN, HUMAN; HISTONE DEACETYLASE;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DRUG APPROVAL; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; IN VITRO STUDY; MEDICINAL CHEMISTRY; MOLECULAR MODEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ACETYLATION; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; HUMAN; METABOLISM;

HISTONE DEACETYLASE 1; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRROLES;

EID: 84986296870     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc-2016-0068     Document Type: Article

References (45)

1. Kouzarides T. Chromatin modifications and their function. Cell 128(4), 693-705 (2007
2. Gregoretti IV, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J. Mol. Biol. 338(1), 17-31 (2004
3. Baylin SB, Ohm JE. Epigenetic gene silencing in cancer-A mechanism for early oncogenic pathway addiction? Nat. Rev. Cancer 6(2), 107-116 (2006
4. Kalveram B, Schmidtke G, Groettrup M. The ubiquitinlike modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition. J. Cell. Sci. 121(Pt 24), 4079-4088 (2008
5. Kovacs JJ, Murphy PJ, Gaillard S, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol. Cell. 18(5), 601-607 (2005
6. Parmigiani RB, Xu WS, Venta-Perez G, et al. HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc. Natl Acad. Sci. USA 105(28), 9633-9638 (2008
7. Zhang X, Yuan Z, Zhang Y, et al. HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol. Cell 27(2), 197-213 (2007
8. Hubbert C, Guardiola A, Shao R, et al. HDAC6 is a microtubule-Associated deacetylase. Nature 417(6887), 455-458 (2002
9. Lee JH, Mahendran A, Yao Y, et al. Development of a histone deacetylase 6 inhibitor and its biological effects. Proc. Natl Acad. Sci. USA 110(39), 15704-15709 (2013
10. Kramer OH, Mahboobi S, Sellmer A. Drugging the HDAC6-HSP90 interplay in malignant cells. Trends Pharmacol. Sci. 35(10), 501-509 (2014
11. Reikvam H, Ersvaer E, Bruserud O. Heat shock protein 90-A potential target in the treatment of human acute myelogenous leukemia. Curr. Cancer Drug Targets 9(6), 761-776 (2009
12. Kawaguchi Y, Kovacs JJ, Mclaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115(6), 727-738 (2003
13. Boyault C, Zhang Y, Fritah S, et al. HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev. 21(17), 2172-2181 (2007
14. Kwon S, Zhang Y, Matthias P. The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev. 21(24), 3381-3394 (2007
15. Bradbury CA, Khanim FL, Hayden R, et al. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia 19(10), 1751-1759 (2005
16. Van Damme M, Crompot E, Meuleman N, et al. HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance. Epigenetics 7(12), 1403-1412 (2012
17. Marquard L, Gjerdrum LM, Christensen IJ, Jensen PB, Sehested M, Ralfkiaer E. Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T-cell lymphoma. Histopathology 53(3), 267-277 (2008
18. Li Y, Shin D, Kwon SH. Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes. FEBS J. 280(3), 775-793 (2013
19. Dallavalle S, Pisano C, Zunino F. Development and therapeutic impact of HDAC6-selective inhibitors. Biochem. Pharmacol. 84(6), 756-765 (2012
20. Muller S, Kramer OH. Inhibitors of HDACs-effective drugs against cancer? Curr. Cancer Drug Targets 10(2), 210-228 (2010
21. Mair B, Kubicek S, Nijman SM. Exploiting epigenetic vulnerabilities for cancer therapeutics. Trends Pharmacol. Sci. 35(3), 136-145 (2014
22. Rambaldi A, Dellacasa CM, Finazzi G, et al. A pilot study of the histone-deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms. Br. J. Haematol. 150(4), 446-455 (2010
23. Sholler GS Currier EA, Dutta A, et al. PCI-24781 (abexinostat), a novel histone deacetylase inhibitor, induces reactive oxygen species-dependent apoptosis and is synergistic with bortezomib in neuroblastoma. J. Cancer Ther. Res. 2 21 2013
24. Butini S Gabellieri E, Brindisi M, et al. A stereoselective approach to peptidomimetic BACE1 inhibitors. Eur. J. Med. Chem. 70 233-247 2013
25. Butini S, Gemma S, Brindisi M, et al. Non-nucleoside inhibitors of human adenosine kinase: synthesis, molecular modeling, and biological studies. J. Med. Chem. 54(5), 1401-1420 (2011
26. Savi L, Brindisi M, Alfano G, et al. Site-directed mutagenesis of key residues unveiled a novel allosteric site on human adenosine kinase for Pyrrolobenzoxa(thia) zepinone non-nucleoside inhibitors. Chem. Biol. Drug Des. 87(1), 112-120 (2016
27. Giovani S, Penzo M, Brogi S, et al. Rational design of the first difluorostatone-based PfSUB1 inhibitors. Bioorg. Med. Chem. Lett. 24(15), 3582-3586 (2014
28. Butini S, Guarino E, Campiani G, et al. Tacrine based human cholinesterase inhibitors: synthesis of peptidic-Tethered derivatives and their effect on potency and selectivity. Bioorg. Med. Chem. Lett. 18(19), 5213-5216 (2008
29. Ghosh AK, Brindisi M, Yen YC, et al. Structure-based design, synthesis and biological evaluation of novel betasecretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand. Bioorg. Med. Chem. Lett. 25(3), 668-672 (2015
30. Brindisi M, Brogi S, Relitti N, et al. Structure-based discovery of the first non-covalent inhibitors of Leishmania major tryparedoxin peroxidase by high throughput docking. Sci. Rep. 5, 9705 (2015
31. Giovani S, Penzo M, Butini S, et al. Plasmodium falciparum subtilisin-like protease 1: discovery of potent difluorostatone-based inhibitors. RSC Adv. 5(29), 22431-22448 (2015
32. Brogi S, Giovani S, Brindisi M, et al. In silico study of subtilisin-like protease 1 (SUB1) from different Plasmodium species in complex with peptidyl-difluorostatones and characterization of potent pan-SUB1 inhibitors. J. Mol. Graph. Model. 64, 121-130 (2016
33. Butini S, Brindisi M, Gemma S, et al. Discovery of potent inhibitors of human and mouse fatty acid amide hydrolases. J. Med. Chem. 55(15), 6898-6915 (2012
34. Butini S, Gemma S, Brindisi M, et al. Identification of a novel arylpiperazine scaffold for fatty acid amide hydrolase inhibition with improved drug disposition properties. Bioorg. Med. Chem. Lett. 23(2), 492-495 (2013
35. Heltweg B, Trapp J, Jung M. In vitro assays for the determination of histone deacetylase activity. Methods 36(4), 332-337 (2005
36. Heltweg B, Dequiedt F, Verdin E, Jung M. Nonisotopic substrate for assaying both human zinc and NAD+-dependent histone deacetylases. Anal. Biochem. 319(1), 42-48 (2003
37. Wegener D, Wirsching F, Riester D, Schwienhorst A. A fluorogenic histone deacetylase assay well suited for highthroughput activity screening. Chem. Biol. 10(1), 61-68 (2003
38. Miles KC, Mays SM, Southerland BK, Auvil TJ, Ketcha DM. The Clauson-Kass pyrrole synthesis under microwave irradiation. ARKIVOC 2009, 181-190 (2009
39. Millard CJ, Watson PJ, Celardo I, et al. Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol. Cell. 51(1), 57-67 (2013
40. Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J. Am. Chem. Soc. 132(31), 10842-10846 (2010
41. Kaliszczak M, Trousil S, Aberg O, Perumal M, Nguyen QD, Aboagye EO. A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth. Br. J. Cancer 108(2), 342-350 (2013
42. Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat. Protoc. 5(4), 725-738 (2010
43. Giovani S, Penzo M, Brogi S, et al. Rational design of the first difluorostatone-based PfSUB1 inhibitors. Bioorg. Med. Chem. Lett. 24(15), 3582-3586 (2014
44. Gemma S, Brogi S, Patil PR, et al. From (+)-epigallocatechin gallate to a simplified synthetic analogue as a cytoadherence inhibitor for P. falciparum. RSC Adv. 4, 4769-4781 (2014
45. Gasser A, Brogi S, Urayama K, et al. Discovery and cardioprotective effects of the first non-peptide agonists of the G protein-coupled prokineticin receptor-1. PLoS ONE 10(4), e0121027 (2015