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      https://www.ias.ac.in/article/fulltext/jcsc/130/06/0063

    • Keywords

       

      Histonedeacetylase (HDAC) inhibitors; hydroxamic acids; 2-oxoindoline; triazole.

    • Abstract

       

      A series of seventeen novel hydroxamic acids incorporating 1-((1H-1,2,3-triazol-4-yl)methyl)-3-hydroxyimino-indolin-2-ones was designed and synthesized. Biological evaluation showed that these hydroxamic acids potently inhibited a class-I isoform of HDACs (HDAC2) with IC50 values in low micromolar range. Several compounds also exhibited good cytotoxicity. Two compounds, 5e and 5f, emerged as the most potent HDAC2 inhibitors with cytotoxicity up to 8-fold more potent than SAHA in three human cancer cell lines,including SW620 (colon cancer), PC3 (prostate cancer) and AsPC-1 (pancreatic cancer). A molecular modeling approach has been carried out which revealed some structure-activity relationships. Further investigation on absorption, distribution, metabolism, excretion and toxicity (ADMET) suggested that compounds 5e and 5f,while showing potent HDAC2 inhibitory bioactivity, hold desirable characteristics for anticancer compounds.

    • Author Affiliations

       

      DO THI MAI DUNG1 PHAM-THE HAI1 DUONG TIEN ANH1 LE-THI-THU HUONG2 NGUYEN THI KIM YEN3 BYUNG WOO HAN3 EUN JAE PARK4 YEO JIN CHOI4 JONG SOON KANG5 VAN-THI-MY HUE1 SANG-BAE HAN4 NGUYEN-HAI NAM1

      1. Hanoi University of Pharmacy, 13-15 Le Thanh Tong, HoanKiem, Hanoi, Vietnam
      2. School of Medicine and Pharmacy, Vietnam National University, 144 XuanThuy, Hanoi, Vietnam
      3. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
      4. College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Korea
      5. Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk, Korea
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    • Supplementary Material

       
  • Journal of Chemical Sciences | News

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