Skip to content
2000
Volume 21, Issue 6
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

HDAC8 is associated with several disease conditions as well as various cancers of several organs and hematological malignancies. To counter such pathophysiological and disease conditions, inhibition of HDAC8 may be a promising approach for anticancer drug development. In this article, a detail of arylcarboxamide-based potential HDAC8 inhibitors has been outlined. Considering their binding pattern of interactions along with the chemical features, effective and selective novel HDAC8 inhibitors can be designed further. Therefore, modification of these compounds provides greater possibilities for the development of novel HDAC8 inhibitors. Nevertheless, structural modification of such arylcarboxamide derivatives may be able to produce potent dual-inhibitory compounds along with HDAC8 inhibition. Thus, this article is quite useful for exploring and identifying several possibilities for arylcarboxamide-based HDAC8 inhibitors. Moreover, it can be concluded that further study of the arylcarboxamide-based HDAC8 inhibitors can be effectively used for the treatment of different cancerous and non-cancerous diseases.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mc/10.2174/0115734064329669241007060848
2024-10-24
2025-10-31

  • From This Site

    /content/journals/mc/10.2174/0115734064329669241007060848
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MoosaviA. Motevalizadeh ArdekaniA. Role of epigenetics in biology and human diseases.Iran. Biomed. J.201620524625810.22045/ibj.2016.01 27377127
     [Google Scholar]
  2. TammenS.A. FrisoS. ChoiS.W. Epigenetics: The link between nature and nurture.Mol. Aspects Med.201334475376410.1016/j.mam.2012.07.018 22906839
     [Google Scholar]
  3. ZhangL. LuQ. ChangC. Epigenetics in health and disease.Adv. Exp. Med. Biol.2020125335510.1007/978‑981‑15‑3449‑2_1 32445090
     [Google Scholar]
  4. NebbiosoA. TambaroF.P. Dell’AversanaC. AltucciL. Cancer epigenetics: Moving forward.PLoS Genet.2018146e100736210.1371/journal.pgen.1007362 29879107
     [Google Scholar]
  5. BersonA. NativioR. BergerS.L. BoniniN.M. Epigenetic regulation in neurodegenerative diseases.Trends Neurosci.201841958759810.1016/j.tins.2018.05.005 29885742
     [Google Scholar]
  6. SunL. ZhangH. GaoP. Metabolic reprogramming and epigenetic modifications on the path to cancer.Protein Cell2022131287791910.1007/s13238‑021‑00846‑7 34050894
     [Google Scholar]
  7. RamaiahM.J. TanguturA.D. ManyamR.R. Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy.Life Sci.202127711950410.1016/j.lfs.2021.119504 33872660
     [Google Scholar]
  8. ShanmugamG. RakshitS. SarkarK. HDAC inhibitors: Targets for tumor therapy, immune modulation and lung diseases.Transl. Oncol.20221610131210.1016/j.tranon.2021.101312 34922087
     [Google Scholar]
  9. LiuS.S. WuF. JinY.M. ChangW.Q. XuT.M. HDAC11: A rising star in epigenetics.Biomed. Pharmacother.202013111060710.1016/j.biopha.2020.110607 32841898
     [Google Scholar]
  10. KhanN.M. HaqqiT.M. Epigenetics in osteoarthritis: Potential of HDAC inhibitors as therapeutics.Pharmacol. Res.2018128737910.1016/j.phrs.2017.08.007 28827187
     [Google Scholar]
  11. HullE.E. MontgomeryM.R. LeyvaK.J. HDAC inhibitors as epigenetic regulators of the immune system: Impacts on cancer therapy and inflammatory diseases.BioMed Res. Int.2016201611510.1155/2016/8797206 27556043
     [Google Scholar]
  12. DingP. MaZ. LiuD. PanM. LiH. FengY. ZhangY. ShaoC. JiangM. LuD. HanJ. WangJ. YanX. Lysine acetylation/deacetylation modification of immune-related molecules in cancer immunotherapy.Front. Immunol.20221386597510.3389/fimmu.2022.865975 35585975
     [Google Scholar]
  13. BanerjeeS. AdhikariN. AminS.A. JhaT. Histone deacetylase 8 (HDAC8) and its inhibitors with selectivity to other isoforms: An overview.Eur. J. Med. Chem.201916421424010.1016/j.ejmech.2018.12.039 30594678
     [Google Scholar]
  14. AdhikariN. JhaT. GhoshB. Dissecting histone deacetylase 3 in multiple disease conditions: Selective inhibition as a promising therapeutic strategy.J. Med. Chem.202164138827886910.1021/acs.jmedchem.0c01676 34161101
     [Google Scholar]
  15. SarkarR. BanerjeeS. AminS.A. AdhikariN. JhaT. Histone deacetylase 3 (HDAC3) inhibitors as anticancer agents: A review.Eur. J. Med. Chem.202019211217110.1016/j.ejmech.2020.112171 32163814
     [Google Scholar]
  16. HoT.C.S. ChanA.H.Y. GanesanA. Thirty years of HDAC inhibitors: 2020 insight and hindsight.J. Med. Chem.20206321124601248410.1021/acs.jmedchem.0c00830 32608981
     [Google Scholar]
  17. AminS.A. AdhikariN. KotagiriS. JhaT. GhoshB. Histone deacetylase 3 inhibitors in learning and memory processes with special emphasis on benzamides.Eur. J. Med. Chem.201916636938010.1016/j.ejmech.2019.01.077 30735902
     [Google Scholar]
  18. AdhikariN. AminS.A. JhaT. Selective and nonselective HDAC8 inhibitors: A therapeutic patent review.Pharm. Pat. Anal.20187625927610.4155/ppa‑2018‑0019 30632447
     [Google Scholar]
  19. GallinariP. MarcoS.D. JonesP. PallaoroM. SteinkühlerC. HDACs, histone deacetylation and gene transcription: From molecular biology to cancer therapeutics.Cell Res.200717319521110.1038/sj.cr.7310149 17325692
     [Google Scholar]
  20. AminS.A. AdhikariN. JhaT. Structure-activity relationships of hydroxamate-based histone deacetylase-8 inhibitors: Reality behind anticancer drug discovery.Future Med. Chem.20179182211223710.4155/fmc‑2017‑0130 29182018
     [Google Scholar]
  21. PulyaS. PatelT. PaulM. AdhikariN. BanerjeeS. RouthollaG. BiswasS. JhaT. GhoshB. Selective inhibition of histone deacetylase 3 by novel hydrazide based small molecules as therapeutic intervention for the treatment of cancer.Eur. J. Med. Chem.202223811447010.1016/j.ejmech.2022.114470 35635949
     [Google Scholar]
  22. PulyaS. AminS.A. AdhikariN. BiswasS. JhaT. GhoshB. HDAC6 as privileged target in drug discovery: A perspective.Pharmacol. Res.202116310527410.1016/j.phrs.2020.105274 33171304
     [Google Scholar]
  23. AdhikariN. AminS.A. TrivediP. JhaT. GhoshB. HDAC3 is a potential validated target for cancer: An overview on the benzamide-based selective HDAC3 inhibitors through comparative SAR/QSAR/QAAR approaches.Eur. J. Med. Chem.20181571127114210.1016/j.ejmech.2018.08.081 30179749
     [Google Scholar]
  24. ChakrabartiA. MelesinaJ. KolbingerF.R. OehmeI. SengerJ. WittO. SipplW. JungM. Targeting histone deacetylase 8 as a therapeutic approach to cancer and neurodegenerative diseases.Future Med. Chem.20168131609163410.4155/fmc‑2016‑0117 27572818
     [Google Scholar]
  25. ChakrabartiA. OehmeI. WittO. OliveiraG. SipplW. RomierC. PierceR.J. JungM. HDAC8: A multifaceted target for therapeutic interventions.Trends Pharmacol. Sci.201536748149210.1016/j.tips.2015.04.013 26013035
     [Google Scholar]
  26. RuzicD. DjokovićN. Srdić-RajićT. EcheverriaC. NikolicK. SantibanezJ.F. Targeting histone deacetylases: Opportunities for cancer treatment and chemoprevention.Pharmaceutics202214120910.3390/pharmaceutics14010209 35057104
     [Google Scholar]
  27. LiG. TianY. ZhuW.G. The roles of histone deacetylases and their inhibitors in cancer therapy.Front. Cell Dev. Biol.2020857694610.3389/fcell.2020.576946 33117804
     [Google Scholar]
  28. BenedettiR. ConteM. AltucciL. Targeting histone deacetylases in diseases: Where Are we?Antioxid. Redox Signal.20152319912610.1089/ars.2013.5776 24382114
     [Google Scholar]
  29. ChenJ. CaoL. MaJ. YueC. ZhuD. AnR. WangX. GuoY. GuB. HDAC8 promotes liver metastasis of colorectal cancer via inhibition of IRF1 and upregulation of SUCNR1.Oxid. Med. Cell. Longev.2022202212310.1155/2022/2815187 36035205
     [Google Scholar]
  30. MenbariM.N. RahimiK. AhmadiA. Mohammadi-YeganehS. ElyasiA. DarvishiN. HosseiniV. AbdiM. Association of HDAC8 expression with pathological findings in triple negative and non-triple negative breast cancer: Implications for diagnosis.Iran. Biomed. J.202024528328910.29252/ibj.24.5.283 32429642
     [Google Scholar]
  31. LiY. LiangR. SunM. LiZ. ShengH. WangJ. XuP. LiuS. YangW. LuB. ZhangS. ShanC. AMPK-dependent phosphorylation of HDAC8 triggers PGM1 expression to promote lung cancer cell survival under glucose starvation.Cancer Lett.2020478829210.1016/j.canlet.2020.03.007 32171858
     [Google Scholar]
  32. KimJ.Y. HanS.Y. YooJ. KimG.W. JeonY.H. LeeS.W. ParkJ. KwonS.H. HDAC8-selective inhibition by PCI-34051 enhances the anticancer effects of ACY-241 in ovarian cancer cells.Int. J. Mol. Sci.20222315864510.3390/ijms23158645 35955780
     [Google Scholar]
  33. VanajaG.R. RamuluH.G. KalleA.M. Overexpressed HDAC8 in cervical cancer cells shows functional redundancy of tubulin deacetylation with HDAC6.Cell Commun. Signal.20181612010.1186/s12964‑018‑0231‑4 29716651
     [Google Scholar]
  34. MahajanM. SuryavanshiS. BhowmickS. AlasmaryF.A. AlmutairiT.M. IslamM.A. Kaul-GhanekarR. Matairesinol, an active constituent of HC9 polyherbal formulation, exhibits HDAC8 inhibitory and anticancer activity.Biophys. Chem.202127310658810.1016/j.bpc.2021.106588 33848944
     [Google Scholar]
  35. SongS. WangY. XuP. YangR. MaZ. LiangS. ZhangG. The inhibition of histone deacetylase 8 suppresses proliferation and inhibits apoptosis in gastric adenocarcinoma.Int. J. Oncol.20154751819182810.3892/ijo.2015.3182 26412386
     [Google Scholar]
  36. ZhangM. YingJ.B. WangS.S. HeD. ZhuH. ZhangC. TangL. LinR. ZhangY. Exploring the binding mechanism of HDAC8 selective inhibitors: Lessons from the modification of Cap group.J. Cell. Biochem.20201215-63162317210.1002/jcb.29583 31907955
     [Google Scholar]
  37. KangY. NianH. RajendranP. KimE. DashwoodW.M. PintoJ.T. BoardmanL.A. ThibodeauS.N. LimburgP.J. LöhrC.V. BissonW.H. WilliamsD.E. HoE. DashwoodR.H. HDAC8 and STAT3 repress BMF gene activity in colon cancer cells.Cell Death Dis.2014510e147610.1038/cddis.2014.422 25321483
     [Google Scholar]
  38. OehmeI. DeubzerH.E. LodriniM. MildeT. WittO. Targeting of HDAC8 and investigational inhibitors in neuroblastoma.Expert Opin. Investig. Drugs200918111605161710.1517/14728220903241658 19780707
     [Google Scholar]
  39. LehmannM. HoffmannM.J. KochA. UlrichS.M. SchulzW.A. NiegischG. Histone deacetylase 8 is deregulated in urothelial cancer but not a target for efficient treatment.J. Exp. Clin. Cancer Res.20143315910.1186/s13046‑014‑0059‑8 25011684
     [Google Scholar]
  40. AhnM.Y. YoonJ.H. Histone deacetylase 8 as a novel therapeutic target in oral squamous cell carcinoma.Oncol. Rep.201737154054610.3892/or.2016.5280 28004115
     [Google Scholar]
  41. KimJ.Y. ChoH. YooJ. KimG.W. JeonY.H. LeeS.W. KwonS.H. HDAC8 deacetylates HIF-1α and enhances its protein stability to promote tumor growth and migration in melanoma.Cancers (Basel)2023154112310.3390/cancers15041123 36831463
     [Google Scholar]
  42. Santos-BarriopedroI. LiY. BahlS. SetoE. HDAC8 affects MGMT levels in glioblastoma cell lines via interaction with the proteasome receptor ADRM1.Genes Cancer2019105-611913310.18632/genesandcancer.197 31798765
     [Google Scholar]
  43. LopezG. BillK.L.J. BidH.K. BraggioD. ConstantinoD. PrudnerB. ZewduA. BatteK. LevD. PollockR.E. HDAC8, a potential therapeutic target for the treatment of malignant peripheral nerve sheath tumors (MPNST).PLoS One2015107e013330210.1371/journal.pone.0133302 26200462
     [Google Scholar]
  44. TianY. WongV.W.S. WongG.L.H. YangW. SunH. ShenJ. TongJ.H.M. GoM.Y.Y. CheungY.S. LaiP.B.S. ZhouM. XuG. HuangT.H.M. YuJ. ToK.F. ChengA.S.L. ChanH.L.Y. Histone deacetylase HDAC8 promotes insulin resistance and β-catenin activation in NAFLD-associated hepatocellular carcinoma.Cancer Res.201575224803481610.1158/0008‑5472.CAN‑14‑3786 26383163
     [Google Scholar]
  45. WattersJ.M. WrightG. SmithM.A. ShahB. WrightK.L. Histone deacetylase 8 inhibition suppresses mantle cell lymphoma viability while preserving natural killer cell function.Biochem. Biophys. Res. Commun.202153477377910.1016/j.bbrc.2020.11.001 33190829
     [Google Scholar]
  46. BalasubramanianS. RamosJ. LuoW. SirisawadM. VernerE. BuggyJ.J. A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas.Leukemia20082251026103410.1038/leu.2008.9 18256683
     [Google Scholar]
  47. AminS.A. AdhikariN. JhaT. Is dual inhibition of metalloenzymes HDAC-8 and MMP-2 a potential pharmacological target to combat hematological malignancies?Pharmacol. Res.201712281910.1016/j.phrs.2017.05.002 28501516
     [Google Scholar]
  48. SpreaficoM. GruszkaA.M. ValliD. MazzolaM. DeflorianG. QuintèA. TotaroM.G. BattagliaC. AlcalayM. MarozziA. PistocchiA. HDAC8: A promising therapeutic target for acute myeloid leukemia.Front. Cell Dev. Biol.2020884410.3389/fcell.2020.00844 33015043
     [Google Scholar]
  49. ZhangP. BrintonL.T. WilliamsK. SherS. OrwickS. Tzung-HueiL. MimsA.S. CossC.C. KulpS.K. YoussefY. ChanW.K. MitchellS. MustonenA. CannonM. PhillipsH. LehmanA.M. KauffmanT. BeaverL. CanfieldD. GrieselhuberN.R. AlinariL. SampathD. YanP. ByrdJ.C. BlachlyJ.S. LapalombellaR. Chan. W.K.; Mitchell. S.; Mustonen, A.; Cannon, M.; Phillips, H.; Lehman, A.M.; Kauffman, T.; Beaver, L.; Canfield, D.; Grieselhuber, N.R.; Alinari, L.; Sampath, D.; Yan, P.; Byrd, J.C.; Blachly, J.S.; Lapalombella, R. Targeting DNA damage repair functions of two histone deacetylases, HDAC8 and SIRT6, sensitizes acute myeloid leukemia to NAMPT inhibition.Clin. Cancer Res.20212782352236610.1158/1078‑0432.CCR‑20‑3724 33542077
     [Google Scholar]
  50. QiJ. SinghS. HuaW.K. CaiQ. ChaoS.W. LiL. LiuH. HoY. McDonaldT. LinA. MarcucciG. BhatiaR. HuangW.J. ChangC.I. KuoY.H. HDAC8 inhibition specifically targets Inv(16) acute myeloid leukemic stem cells by restoring p53 acetylation.Cell Stem Cell201517559761010.1016/j.stem.2015.08.004 26387755
     [Google Scholar]
  51. ZhaoT. KeeH.J. BaiL. KimM.K. KeeS.J. JeongM.H. Selective HDAC8 inhibition attenuates isoproterenol-induced cardiac hypertrophy and fibrosis via p38 MAPK pathway.Front. Pharmacol.20211267775710.3389/fphar.2021.677757 33959033
     [Google Scholar]
  52. YanM. ChenC. GongW. YinZ. ZhouL. ChaugaiS. WangD.W. miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8.Cardiovasc. Res.2015105334035210.1093/cvr/cvu254 25504627
     [Google Scholar]
  53. SaitoS. ZhuangY. SuzukiT. OtaY. BatemanM.E. AlkhatibA.L. MorrisG.F. LaskyJ.A. HDAC8 inhibition ameliorates pulmonary fibrosis.Am. J. Physiol. Lung Cell. Mol. Physiol.20193161L175L18610.1152/ajplung.00551.2017 30358439
     [Google Scholar]
  54. SpreaficoM. CaforaM. BragatoC. CapitanioD. MarascaF. BodegaB. De PalmaC. MoraM. GelfiC. MarozziA. PistocchiA. Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy.Pharmacol. Res.202117010575010.1016/j.phrs.2021.105750 34214631
     [Google Scholar]
  55. XiaoT. FuY. ZhuW. XuR. XuL. ZhangP. DuY. ChengJ. JiangH. HDAC8, a potential therapeutic target, regulates proliferation and differentiation of bone marrow stromal cells in fibrous dysplasia.Stem Cells Transl. Med.20198214816110.1002/sctm.18‑0057 30426726
     [Google Scholar]
  56. DeardorffM.A. PorterN.J. ChristiansonD.W. Structural aspects of HDAC8 mechanism and dysfunction in Cornelia de Lange syndrome spectrum disorders.Protein Sci.201625111965197610.1002/pro.3030 27576763
     [Google Scholar]
  57. MioC. PassonN. FogolariF. CesarioC. NovelliA. PittiniC. DamanteG. A novel de novo HDAC8 missense mutation causing Cornelia de Lange syndrome.Mol. Genet. Genomic Med.202199e161210.1002/mgg3.1612 34342180
     [Google Scholar]
  58. LeeC.H. ChoiY. ChoH. BangI.H. HaoL. LeeS.O. JeonR. BaeE.J. ParkB.H. Histone deacetylase 8 inhibition alleviates cholestatic liver injury and fibrosis.Biochem. Pharmacol.202118311431210.1016/j.bcp.2020.114312 33130126
     [Google Scholar]
  59. ZhangY. ZouJ. TolbertE. ZhaoT.C. BaylissG. ZhuangS. Identification of histone deacetylase 8 as a novel therapeutic target for renal fibrosis.FASEB J.20203467295731010.1096/fj.201903254R 32281211
     [Google Scholar]
  60. MarekM. KannanS. HauserA.T. Moraes MourãoM. CabyS. CuraV. StolfaD.A. SchmidtkunzK. LancelotJ. AndradeL. RenaudJ.P. OliveiraG. SipplW. JungM. CavarelliJ. PierceR.J. RomierC. Structural basis for the inhibition of histone deacetylase 8 (HDAC8), a key epigenetic player in the blood fluke Schistosoma mansoni.PLoS Pathog.201399e100364510.1371/journal.ppat.1003645 24086136
     [Google Scholar]
  61. NoceB. Di BelloE. ZwergelC. FioravantiR. ValenteS. RotiliD. MasottiA. Salik Zeya AnsariM. TrisciuoglioD. ChakrabartiA. RomierC. RobaaD. SipplW. JungM. HäberliC. KeiserJ. MaiA. Chemically diverse S. ansoni HDAC8 inhibitors reduce viability in worm larval and adult stages.ChemMedChem2023183e20220051010.1002/cmdc.202200510 36250286
     [Google Scholar]
  62. YoonJ.I. ChoH. JeonR. SungM.K. Therapeutic efficacy of novel HDAC inhibitors SPA3052 and SPA3074 against intestinal inflammation in a murine model of colitis.Pharmaceuticals (Basel)20221512151510.3390/ph15121515 36558966
     [Google Scholar]
  63. ZhouX. ChenH. ShiY. LiJ. MaX. DuL. HuY. TaoM. ZhongQ. YanD. ZhuangS. LiuN. Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization.Front. Immunol.202314113733210.3389/fimmu.2023.1137332 36911746
     [Google Scholar]
  64. XiaB. LuJ. WangR. YangZ. ZhouX. HuangP. miR-21-3p regulates influenza a virus replication by targeting histone deacetylase-8.Front. Cell. Infect. Microbiol.2018817510.3389/fcimb.2018.00175 29888214
     [Google Scholar]
  65. ChenY. PanC. LuY. MiaoY. XiongB. HDAC8 drives spindle organization during meiotic maturation of porcine oocytes.Cell Prolif.20215410e1311910.1111/cpr.13119 34435400
     [Google Scholar]
  66. AminS.A. AdhikariN. JhaT. Structure-activity relationships of HDAC8 inhibitors: Non-hydroxamates as anticancer agents.Pharmacol. Res.201813112814210.1016/j.phrs.2018.03.001 29514055
     [Google Scholar]
  67. MottamalM. ZhengS. HuangT. WangG. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents.Molecules20152033898394110.3390/molecules20033898 25738536
     [Google Scholar]
  68. SomozaJ.R. SkeneR.J. KatzB.A. MolC. HoJ.D. JenningsA.J. LuongC. ArvaiA. BuggyJ.J. ChiE. TangJ. SangB.C. VernerE. WynandsR. LeahyE.M. DouganD.R. SnellG. NavreM. KnuthM.W. SwansonR.V. McReeD.E. TariL.W. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases.Structure20041271325133410.1016/j.str.2004.04.012 15242608
     [Google Scholar]
  69. MarekM. ShaikT.B. HeimburgT. ChakrabartiA. LancelotJ. Ramos-MoralesE. Da VeigaC. KalininD. MelesinaJ. RobaaD. SchmidtkunzK. SuzukiT. HollR. EnnifarE. PierceR.J. JungM. SipplW. RomierC. Characterization of histone deacetylase 8 (HDAC8) selective inhibition reveals specific active site structural and functional determinants.J. Med. Chem.20186122100001001610.1021/acs.jmedchem.8b01087 30347148
     [Google Scholar]
  70. KozikowskiA.P. ChenY. GaysinA. ChenB. D’AnnibaleM.A. SutoC.M. LangleyB.C. Functional differences in epigenetic modulators-superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies.J. Med. Chem.200750133054306110.1021/jm070178x 17539623
     [Google Scholar]
  71. ChenY. Lopez-SanchezM. SavoyD.N. BilladeauD.D. DowG.S. KozikowskiA.P. A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum.J. Med. Chem.200851123437344810.1021/jm701606b 18494463
     [Google Scholar]
  72. KozikowskiA.P. TapadarS. LuchiniD.N. KimK.H. BilladeauD.D. Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: A new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6.J. Med. Chem.200851154370437310.1021/jm8002894 18642892
     [Google Scholar]
  73. HeR. ChenY. ChenY. OugolkovA.V. ZhangJ.S. SavoyD.N. BilladeauD.D. KozikowskiA.P. Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anticancer agents.J. Med. Chem.20105331347135610.1021/jm901667k 20055418
     [Google Scholar]
  74. HeB. VelaparthiS. PieffetG. PenningtonC. MaheshA. HolzleD.L. BrunsteinerM. van BreemenR. BlondS.Y. PetukhovP.A. Binding ensemble profiling with photoaffinity labeling (BEProFL) approach: Mapping the binding poses of HDAC8 inhibitors.J. Med. Chem.200952227003701310.1021/jm9005077 19886628
     [Google Scholar]
  75. NeelarapuR. HolzleD.L. VelaparthiS. BaiH. BrunsteinerM. BlondS.Y. PetukhovP.A. Design, synthesis, docking, and biological evaluation of novel diazide-containing isoxazole- and pyrazole-based histone deacetylase probes.J. Med. Chem.201154134350436410.1021/jm2001025 21548582
     [Google Scholar]
  76. VaidyaA.S. NeelarapuR. MadriagaA. BaiH. MendoncaE. AbdelkarimH. van BreemenR.B. BlondS.Y. PetukhovP.A. Novel histone deacetylase 8 ligands without a zinc chelating group: Exploring an ‘upside-down’ binding pose.Bioorg. Med. Chem. Lett.201222216621662710.1016/j.bmcl.2012.08.104 23010266
     [Google Scholar]
  77. ZhangY. FengJ. JiaY. XuY. LiuC. FangH. XuW. Design, synthesis and primary activity assay of tripeptidomimetics as histone deacetylase inhibitors with linear linker and branched cap group.Eur. J. Med. Chem.201146115387539710.1016/j.ejmech.2011.08.045 21924799
     [Google Scholar]
  78. ZhangL. WangX. LiX. ZhangL. XuW. Discovery of a series of hydroximic acid derivatives as potent histone deacetylase inhibitors.J. Enzyme Inhib. Med. Chem.201429458258910.3109/14756366.2013.827678 24059701
     [Google Scholar]
  79. AndrianovV. GailiteV. LolaD. LozaE. SemenikhinaV. KalvinshI. FinnP. PetersenK.D. RitchieJ.W.A. KhanN. TumberA. CollinsL.S. VadlamudiS.M. BjörklingF. SehestedM. Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR.Eur. J. Med. Chem.20094431067108510.1016/j.ejmech.2008.06.020 18672316
     [Google Scholar]
  80. WangH. LimZ.Y. ZhouY. NgM. LuT. LeeK. SangthongpitagK. GohK.C. WangX. WuX. KhngH.H. GohS.K. OngW.C. BondayZ. SunE.T. Acylurea connected straight chain hydroxamates as novel histone deacetylase inhibitors: Synthesis, SAR, and in vivo antitumor activity.Bioorg. Med. Chem. Lett.201020113314332110.1016/j.bmcl.2010.04.041 20451378
     [Google Scholar]
  81. MarekL. HamacherA. HansenF.K. KunaK. GohlkeH. KassackM.U. KurzT. Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells.J. Med. Chem.201356242743610.1021/jm301254q 23252603
     [Google Scholar]
  82. WagnerF.F. OlsonD.E. GaleJ.P. KayaT. WeïwerM. AidoudN. ThomasM. DavoineE.L. LemercierB.C. ZhangY.L. HolsonE.B. Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif.J. Med. Chem.20135641772177610.1021/jm301355j 23368884
     [Google Scholar]
  83. TashimaT. MurataH. KodamaH. Design and synthesis of novel and highly-active pan-histone deacetylase (pan-HDAC) inhibitors.Bioorg. Med. Chem.201422143720373110.1016/j.bmc.2014.05.001 24864038
     [Google Scholar]
  84. RajiI. YaduduF. JaneiraE. FathiS. SzymczakL. KornackiJ.R. KomatsuK. LiJ.D. MrksichM. OyelereA.K. Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase.Bioorg. Med. Chem.20172531202121810.1016/j.bmc.2016.12.032 28057407
     [Google Scholar]
  85. WangX. LiX. LiJ. HouJ. QuY. YuC. HeF. XuW. WuJ. Design, synthesis, and preliminary bioactivity evaluation of N1 ‐hydroxyterephthalamide derivatives with indole cap as novel histone deacetylase inhibitors.Chem. Biol. Drug Des.2017891384610.1111/cbdd.12819 27416889
     [Google Scholar]
  86. GuerrantW. PatilV. CanzoneriJ.C. OyelereA.K. Dual targeting of histone deacetylase and topoisomerase II with novel bifunctional inhibitors.J. Med. Chem.20125541465147710.1021/jm200799p 22260166
     [Google Scholar]
  87. SantoL. HideshimaT. KungA.L. TsengJ.C. TamangD. YangM. JarpeM. van DuzerJ.H. MazitschekR. OgierW.C. CirsteaD. RodigS. EdaH. ScullenT. CanaveseM. BradnerJ. AndersonK.C. JonesS.S. RajeN. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma.Blood2012119112579258910.1182/blood‑2011‑10‑387365 22262760
     [Google Scholar]
  88. TrivediP. AdhikariN. AminS.A. BobdeY. GaneshR. JhaT. GhoshB. Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity.Eur. J. Pharm. Sci.201913810504610.1016/j.ejps.2019.105046 31421254
     [Google Scholar]
  89. AminS.A. TrivediP. AdhikariN. RouthollaG. VijayasarathiD. DasS. GhoshB. JhaT. Quantitative activity–activity relationship (QAAR) driven design to develop hydroxamate derivatives of pentanoic acids as selective HDAC8 inhibitors: Synthesis, biological evaluation and binding mode of interaction studies.New J. Chem.20214537171491716210.1039/D1NJ02636D
     [Google Scholar]
  90. PatelH.K. SiklosM.I. AbdelkarimH. MendoncaE.L. VaidyaA. PetukhovP.A. ThatcherG.R.J. A chimeric SERM-histone deacetylase inhibitor approach to breast cancer therapy.ChemMedChem20149360261310.1002/cmdc.201300270 23956109
     [Google Scholar]
  91. HalderA.K. MallickS. ShikhaD. SahaA. SahaK.D. JhaT. Design of dual MMP-2/HDAC-8 inhibitors by pharmacophore mapping, molecular docking, synthesis and biological activity.RSC Advances2015588723737238610.1039/C5RA12606A
     [Google Scholar]
  92. DuttaS. HalderA.K. AdhikariN. AminS.A. DasS. SahaA. JhaT. Synthesis, anticancer activity, structure-activity relationship and binding mode of interaction studies of substituted pentanoic acids.Future Med. Chem.201911141679170210.4155/fmc‑2018‑0361 31370697
     [Google Scholar]
  93. DattaS. HalderA.K. AdhikariN. AminS.A. DasS. JhaT. Synthesis, anticancer activity, SAR and binding mode of interaction studies of substituted pentanoic acids: part II.Future Med. Chem.2022141173410.4155/fmc‑2021‑0049 34818903
     [Google Scholar]
  94. MuthyalaR. ShinW.S. XieJ. ShamY.Y. Discovery of 1-hydroxypyridine-2-thiones as selective histone deacetylase inhibitors and their potential application for treating leukemia.Bioorg. Med. Chem. Lett.201525194320432410.1016/j.bmcl.2015.07.065 26264503
     [Google Scholar]
  95. SuzukiN. SuzukiT. OtaY. NakanoT. KuriharaM. OkudaH. YamoriT. TsumotoH. NakagawaH. MiyataN. Design, synthesis, and biological activity of boronic acid-based histone deacetylase inhibitors.J. Med. Chem.20095292909292210.1021/jm900125m 19419205
     [Google Scholar]
  96. BottaC.B. CabriW. CiniE. De CesareL. FattorussoC. GianniniG. PersicoM. PetrellaA. RondinelliF. RodriquezM. RussoA. TaddeiM. Oxime amides as a novel zinc binding group in histone deacetylase inhibitors: synthesis, biological activity, and computational evaluation.J. Med. Chem.20115472165218210.1021/jm101373a 21417297
     [Google Scholar]
  97. StunkelW. WangH. YinZ. Biaryl linked hydroxamates: Preparation and pharmaceutical applications.WO Patent 20050401612005
  98. LimZ.-Y. WangH. ZhouY. Acylurea connected and sulfonylurea connected hydroxamates.WO Patent 20050401012005
  99. AshwellM.A. TandonM. NamdewN.D. LapierreJ.M. LiuY. WuH. Hdac inhibitors.WO Patent 20090264462009
  100. OyelereA. Inhibitors and methods of making and using thereof.U.S. Patent 201001976222010
  101. Cossío MoraF.P. OlascoagaA.Z. SalazarY.I.V. LarzabalE.S.S. AnsaD.O. MargalefM.C.M. Aldaba ArévaloF. New histone deacetylase inhibitors based simultaneously on trisubstituted 1h-pyrroles and aromatic and heteroaromatic spacers.EP Patent 2305643A12011
  102. BanerjeeS. GhoshB. JhaT. AdhikariN. A patent review of histone deacetylase 8 (HDAC8) inhibitors (2013–present).Expert Opin. Ther. Pat.202434101019104510.1080/13543776.2024.2391289 39121339
     [Google Scholar]
/content/journals/mc/10.2174/0115734064329669241007060848
Loading
Arylcarboxamide Derivatives as Promising HDAC8 Inhibitors: An Overview in Light of Structure-activity Relationship and Binding Mode of Interaction Analysis
Med. Chem. 21, 471 (2025); https://doi.org/10.2174/0115734064329669241007060848
/content/journals/mc/10.2174/0115734064329669241007060848
/content/journals/mc/10.2174/0115734064329669241007060848
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): arylcarboxamide; binding mode of interaction; Cancer; HDAC8; HDAC8 inhibitor; structure-activity relationship (SAR)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test