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Future Medicinal Chemistry Volume 16, 2024 - Issue 7
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Research Article

Design, Synthesis and Mechanistic Study of New Dual Targeting HDAC/Tubulin Inhibitors

Mona S El-Zoghbi1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Menoufia University, EgyptORCID Iconhttps://orcid.org/0000-0003-1521-4581View further author information
ORCID Icon,
Amr KA Bass1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Menoufia University, EgyptORCID Iconhttps://orcid.org/0000-0002-0588-0073View further author information
ORCID Icon,
Gamal El-Din A Abuo-Rahma2 Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt;3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New Minia, Minia, EgyptORCID Iconhttps://orcid.org/0000-0003-3908-1832View further author information
ORCID Icon,
Mamdouh FA Mohamed4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag, 82524, EgyptORCID Iconhttps://orcid.org/0000-0002-7046-1799View further author information
ORCID Icon,
Mohamed Badr5 Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Menoufia, EgyptORCID Iconhttps://orcid.org/0000-0003-3596-1664View further author information
ORCID Icon,
Hanan A AL-Ghulikah6 Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, PO Box 84428, Riyadh, 11671, Saudi ArabiaORCID Iconhttps://orcid.org/0000-0002-3253-9698View further author information
ORCID Icon &
El-Shimaa MN Abdelhafez7 Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519, EgyptCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-0078-5261View further author information
ORCID Icon show all
Pages 601-622 | Received 12 Nov 2023, Accepted 14 Feb 2024, Published online: 04 Mar 2024

References

  • Dawson MA , KouzaridesTJC. Cancer epigenetics: from mechanism to therapy. Cell150(1), 12–27 (2012).
  • Ribich S , HarveyD, CopelandRaJCCB. Drug discovery and chemical biology of cancer epigenetics. Cell Chem. Biol.24(9), 1120–1147 (2017).
  • Riddhidev B , EndriK, SabitriLet al. Rational design of metabolically stable HDAC inhibitors: an overhaul of trifluoromethyl ketones. Eur. J. Med. Chem.244, 114807 (2022).
  • Rodd AL , VerverisK, KaragiannisTCJ. Current and emerging therapeutics for cutaneous T-cell lymphoma: histone deacetylase inhibitors. Lymphoma2012, 1–10 (2012).
  • Ho TC , ChanAH, GanesanAJ. Thirty years of HDAC inhibitors: 2020 insight and hindsight. J. Med. Chem.63(21), 12460–12484 (2020).
  • Witt O , DeubzerHE, MildeT, OehmeIJ. HDAC family: what are the cancer relevant targets?Cancer Lett.277(1), 8–21 (2009).
  • Zhao L , LiangQ, HeYet al. HDAC/JAK dual target inhibitors of cancer-related targets: the success of nonclearable linked pharmacophore mode. Bioorg. Chem.129, 106181 (2022).
  • Nepali K , Wua–c, LoW-Let al. Rationally designed donepezil-based hydroxamates modulate Sig-1R and HDAC isoforms to exert anti-glioblastoma effects. Eur. J. Med. Chem.248, 115054 (2023).
  • Chen C , ChuH, WangAet al. Discovery of 2, 5-diphenyl-1, 3, 4-thiadiazole derivatives as HDAC inhibitors with DNA binding affinity. Eur. J. Med. Chem.241, 114634 (2022).
  • Deangelo DJ , MesaRA, FiskusWet al. Phase II trial of panobinostat, an oral pan-deacetylase inhibitor in patients with primary myelofibrosis, post–essential thrombocythaemia, and post–polycythaemia vera myelofibrosis. Br. J. Haematol.162(3), 326–335 (2013).
  • Liu Q , ZhangB, WangY, WangX, GouSJEJOMC. Discovery of phthalazino [1, 2-b]-quinazolinone derivatives as multi-target HDAC inhibitors for the treatment of hepatocellular carcinoma via activating the p53 signal pathway. Eur. J. Med. Chem.229, 114058 (2022).
  • Sunil D , RKamath PJMRIMC. Indole based tubulin polymerization inhibitors: an update on recent developments. Mini Rev. Med. Chem.16(18), 1470–1499 (2016).
  • Wang Q , ArnstKE, WangYet al. Structure-guided design, synthesis, and biological evaluation of (2-(1 H-indol-3-yl)-1 H-imidazol-4-yl)(3, 4, 5-trimethoxyphenyl) methanone (ABI-231) analogues targeting the colchicine binding site in tubulin. J. Med. Chem.62(14), 6734–6750 (2019).
  • Gao F , LiangY, ZhouP, ChengJ, DingK, WangYJEJOMC. Design, synthesis, antitumor activities and biological studies of novel diaryl substituted fused heterocycles as dual ligands targeting tubulin and katanin. Eur. J. Med. Chem.178, 177–194 (2019).
  • Tang H , ChengJ, LiangY, WangYJEJOMC. Discovery of a chiral fluorinated azetidin-2-one as a tubulin polymerisation inhibitor with potent antitumour efficacy. Eur. J. Med. Chem.197, 112323 (2020).
  • Tang H , LiangY, ChengJ, DingK, WangYJEJOMC. Bifunctional chiral selenium-containing 1, 4-diarylazetidin-2-ones with potent antitumor activities by disrupting tubulin polymerization and inducing reactive oxygen species production. Eur. J. Med. Chem.221, 113531 (2021).
  • Ren W , DengY, WardJDet al. Synthesis and biological evaluation of structurally diverse 6-aryl-3-aroyl-indole analogues as inhibitors of tubulin polymerization. Eur. J. Med. Chem.263, 115794 (2024).
  • Wang C , ZhangY, YangSet al. Design, synthesis, and bioevaluation of 1 h-pyrrolo [3, 2-c] pyridine derivatives as colchicine-binding site inhibitors with potent anticancer activities. Journal of Enzyme Inhibition Medicinal Chemistry39(1), 2302320 (2024).
  • Peng X , ChenJ, LiLet al. Efficient synthesis and bioevaluation of novel dual tubulin/histone deacetylase 3 inhibitors as potential anticancer agents. J. Med. Chem.64(12), 8447–8473 (2021).
  • Zheng S , ZhongQ, MottamalMet al. Design, synthesis, and biological evaluation of novel pyridine-bridged analogues of combretastatin-A4 as anticancer agents. J. Med. Chem.57(8), 3369–3381 (2014).
  • Ryad N , MyA-S, IsmailMM, ElMeligie SJC, BulletinP. Design, synthesis and screening of 4, 6-diaryl pyridine and pyrimidine derivatives as potential cytotoxic molecules. Chem. Pharmaceut. Bull.66(10), 939–952 (2018).
  • Bass AK , AbdelhafezE, El-ZoghbiMet al. 3-Cyano-2-oxa-pyridines: a promising template for diverse pharmacological activities. J. Adv. Biomed. Pharmaceut. Sci.4(2), 81–86 (2021).
  • Liu Z , TongY, LiuYet al. Effects of suberoylanilide hydroxamic acid (SAHA) combined with paclitaxel (PTX) on paclitaxel-resistant ovarian cancer cells and insights into the underlying mechanisms. Cancer Cell Int.14(1), 1–11 (2014).
  • Chao M-W , LaiM-J, LiouJ-Pet al. The synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo. J. Hematol. Oncol.8, 1–15 (2015).
  • Shu C , Sabi-MoukaEMB, YangW, LiZ, DingLJRA. Effects of paclitaxel (PTX) prodrug-based self-assembly peptide hydrogels combined with suberoylanilide hydroxamic acid (SAHA) for PTX-resistant cancer and synergistic antitumor therapy. RSC Adv.6(103), 100765–100771 (2016).
  • Wang B , ChenX, GaoJet al. Anti-tumor activity evaluation of novel tubulin and HDAC dual-targeting inhibitors. Bioorg. Med. Chem. Lett.29(18), 2638–2645 (2019).
  • Lai M-J , OjhaR, LinM-Het al. 1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase. Eur. J. Med. Chem.162, 612–630 (2019).
  • Peng X , ChenJ, LiLet al. Efficient synthesis and bioevaluation of novel dual tubulin/histone deacetylase 3 inhibitors as potential anticancer agents. J. Med. Chem.64(12), 8447–8473 (2021).
  • Zhang X , ZhangJ, TongLet al. The discovery of colchicine-SAHA hybrids as a new class of antitumor agents. Bioorg. Med. Chem.21(11), 3240–3244 (2013).
  • Tang H , LiangY, ShenHet al. Discovery of a 2, 6-diarylpyridine-based hydroxamic acid derivative as novel histone deacetylase 8 and tubulin dual inhibitor for the treatment of neuroblastoma. Bioorg. Chem.128, 106112 (2022).
  • Hauguel C , DucellierS, ProvotOet al. Design, synthesis and biological evaluation of quinoline-2-carbonitrile-based hydroxamic acids as dual tubulin polymerization and histone deacetylases inhibitors. Eur. J. Med. Chem.240, 114573 (2022).
  • Sun M , QinJ, KangYet al. 2-Methoxydiol derivatives as new tubulin and HDAC dual-targeting inhibitors, displaying antitumor and antiangiogenic response. Bioorg. Chem.120, 105625 (2022).
  • Di Bello E , SianV, BontempiGet al. Novel pyridine-containing histone deacetylase inhibitors strongly arrest proliferation, induce apoptosis and modulate miRNAs in cancer cells. Eur. J. Med. Chem.247, 115022 (2023).
  • Bass AK , NageebE-SM, El-ZoghbiMS, MohamedMF, BadrM, Abuo-RahmaGE-DA. Utilization of cyanopyridine in design and synthesis of first-in-class anticancer dual acting PIM-1 kinase/HDAC inhibitors. Bioorg. Chem.119, 105564 (2022).
  • NCI-60 Screening Methodology | NCI-60 Human Tumor Cell Lines Screen | Discovery & Development Services | Developmental Therapeutics Program (DTP). cancer.gov
  • Abcam . HDAC Inhibitor Drug Screening Kit (Fluorometric). www.biovision.com/documentation/datasheets/K340.pdf
  • BPS Bioscience . HDAC1 Assay. www.bpsbioscience.com/pub/media/wysiwyg/HDACs/53001_1.pdf
  • BPS Bioscience . Fluorogenic HDAC6 Assay. www.bpsbioscience.com/pub/media/wysiwyg/HDACs/50076-1_96_Reactions_.pdf
  • Lo KK-W , LeeTK-M, LauJS-Y, PoonW-L, ChengS-H. Luminescent biological probes derived from ruthenium (II) estradiol polypyridine complexes. Inorgan. Chem.47(1), 200–208 (2008).
  • Van Meerloo J , KaspersGJ, CloosJJCCCM, Protocols. Cell sensitivity assays: the MTT assay. Cancer Cell Culture: Methods Protocols731, 237–245 (2011).
  • Turky A , BayoumiAH, GhiatyA, El-AzabAS, AlaaA-M, AbulkhairHSJBC. Design, synthesis, and antitumor activity of novel compounds based on 1, 2, 4-triazolophthalazine scaffold: apoptosis-inductive and PCAF-inhibitory effects. Bioorg. Chem.101, 104019 (2020).
  • Andree H , ReutelingspergerC, HauptmannR, HemkerHC, HermensWT, WillemsGJJOBC. Binding of vascular anticoagulant alpha (VAC alpha) to planar phospholipid bilayers. J. Biol. Chem.265(9), 4923–4928 (1990).
  • El-Sayed HA , OufNH, MoustafaAH. An efficient and facile multicomponent synthesis of 4, 6-diarylpyridine derivatives under solvent-free conditions. Res. Chem. Intermed.40(1), 407–412 (2014).
  • Marzouk AA , BassAK, AhmedMSet al. Design, synthesis and anticonvulsant activity of new imidazolidindione and imidazole derivatives. Bioorg. Chem.101, 104020 (2020).
  • Mohamed MFA , ShaykoonMSA, AbdelrahmanMH, ElsadekBEM, AboraiaAS, Abuo-RahmaG. Design, synthesis, docking studies and biological evaluation of novel chalcone derivatives as potential histone deacetylase inhibitors. Bioorg. Chem.72, 32–41 (2017).
  • Mohamed MFA , YoussifBGM, ShaykoonMSAet al. Utilization of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinone as a cap moiety in design of novel histone deacetylase inhibitors. Bioorg. Chem.91, 103127 (2019).
  • Dawood M , FleischerE, KlingerA, BringmannG, ShanL, EfferthTJPR. Inhibition of cell migration and induction of apoptosis by a novel class II histone deacetylase inhibitor, MCC2344. Pharmacol. Res.160, 105076 (2020).
  • Vermes I , HaanenC, Steffens-NakkenH, ReutellingspergerC. A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. J. Immunol. Methods184(1), 39–51 (1995).
  • Ibrahim TS , ShehaTA, Abo-DyaNEet al. Design, synthesis and anticancer activity of novel valproic acid conjugates with improved histone deacetylase (HDAC) inhibitory activity. Bioorg. Chem.99, 103797 (2020).
  • Al-Sanea MM , GotinaL, MohamedMFet al. Design, synthesis and biological evaluation of new HDAC1 and HDAC2 inhibitors endowed with ligustrazine as a novel cap moiety. Drug Design Develop. Ther.14, 497–508 (2020).
  • Abdelbaset MS , Abuo-RahmaGE-DA, AbdelrahmanMHet al. Novel pyrrol-2 (3H)-ones and pyridazin-3 (2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors. Bioorg. Chem.80, 151–163 (2018).

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