2. Academic Validation
  3. Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics

Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics

  • Sci Rep. 2025 Sep 26;15(1):33307. doi: 10.1038/s41598-025-02774-6.
Amer H Tarawneh 1,  Salah A Al-Trawneh 2 3,  Talha Z Yesiloglu 4,  Matthes Zessin 5,  Dina Robaa 4,  Cyril Barinka 6,  Mike Schutkowski 5,  Wolfgang Sippl 7,  Samir A Ross 8 9
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Tafila Technical University, P.O. Box 179, Tafila, 66110, Jordan. amer.tarawneh@ttu.edu.jo.
  • 2 Chemistry Department, Faculty of Science, Mu'tah University, Karak, 61710, Jordan. laratr@mutah.edu.jo.
  • 3 National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. laratr@mutah.edu.jo.
  • 4 Institute of Pharmacy, Martin-Luther University of Halle-Wittenberg, 06120, Halle/Saale, Germany.
  • 5 Institute of Biotechnology, Martin-Luther University of Halle-Wittenberg, 06120, Halle/Saale, Germany.
  • 6 Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50, Vestec, Czech Republic.
  • 7 Institute of Pharmacy, Martin-Luther University of Halle-Wittenberg, 06120, Halle/Saale, Germany. wolfgang.sippl@pharmazie.uni-halle.de.
  • 8 National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. sross@olemiss.edu.
  • 9 Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. sross@olemiss.edu.
PMID: 41006293 DOI: 10.1038/s41598-025-02774-6
Abstract

Histone deacetylase (HDAC) inhibitors represent a promising class of anti-cancer agents that play a key role in both epigenetic and non-epigenetic regulation, leading to Cancer cell death, Apoptosis, and cell cycle arrest. This study synthesized novel bicyclic hydroxamic acid derivatives and evaluated their inhibitory and selectivity activity against class I and IIb HDACs. Our findings demonstrate that Compound 2e specifically inhibits HDAC10 with high selectivity over HDAC6, while shows no significant impact on class I HDACs. Compound 2a exhibited the most potant inhibitory activity against HDAC10, with IC50 0.41 ± 0.02 nM. In contrast, Compound 2f revealed a preference toward HDAC6, with an IC50 value of 2.5 ± 0.3 nM. Compounds 2c and 2d demonstrated high selectivity toward class IIb over class I HDACs. Docking and molecular dynamics studies revealed that compound 2a fits well into the active site of HDAC10, forming stable and strong interactions with key residues F204, D94, W205, and E274 in HDAC10. In addition, we assessed the anti-proliferative activity these compounds against a panel of four human solid tumor cell lines. To evaluate their selectivity, non-cancerous kidney cell lines (LLC-PK1 and VERO) were employed to determine the effects of these compounds on normal cell proliferation.

Keywords

HDAC10 inhibitors; Histone deacetylases; Molecular docking; Molecular dynamics; Tumor cell lines.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-178948
    HDAC10抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z