2. Academic Validation
  3. Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect

Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect

  • Bioorg Med Chem. 2023 May 15:86:117300. doi: 10.1016/j.bmc.2023.117300.
Kapil Kumar 1,  Ranjana Das 1,  Barsha Thapa 1,  Bharti Rakhecha 2,  Sapna Srivastava 2,  Kumari Savita 1,  Monazza Israr 1,  Debabrata Chanda 3,  Dibyendu Banerjee 4,  Karuna Shanker 3,  D U Bawankule 3,  Benedetta Santini 5,  Maria Luisa Di Paolo 6,  Lisa Dalla Via 7,  Daniele Passarella 5,  Arvind Singh Negi 8
Affiliations

Affiliations

  • 1 CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow 226015, India.
  • 2 CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
  • 3 CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow 226015, India; Academy of Science and Innovative Research (AcSIR), Ghaziabad, U.P. 201002, India.
  • 4 CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India; Academy of Science and Innovative Research (AcSIR), Ghaziabad, U.P. 201002, India.
  • 5 Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
  • 6 Department of Molecular Medicine, University of Padova, via G. Colombo 3, 35131 Padova, Italy.
  • 7 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via F. Marzolo 5, 35131 Padova, Italy.
  • 8 CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow 226015, India; Academy of Science and Innovative Research (AcSIR), Ghaziabad, U.P. 201002, India. Electronic address: as.negi@cimap.res.in.
PMID: 37146520 DOI: 10.1016/j.bmc.2023.117300
Abstract

Abnormal Epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for Anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as Anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36-3.27 µM) and high potency against HDAC 6 Enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted Anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.

Keywords

Acute oral toxicity; Anticancer; Antiinflammatory; Histone deacetylases; Leukemia; Microtubules.

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