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Exploration of some indole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents

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Abstract

In our search for novel small molecules targeting histone deacetylases, we have designed and synthesized a series of novel hydroxamic acids incorporating indole moiety as a cap group (3a–l). Biological evaluation showed that these hydroxamic acids potently inhibited HDAC2 with IC50 values in submicromolar range and up to tenfold (compound 3j) better than that of SAHA (also known as suberoylanilide hydroxamic acid). In four human cancer cell lines [SW620 (colon), PC-3 (prostate), AsPC-1 (pancreatic), NCI-H23 (lung)], the synthesized compounds that exhibited potent cytotoxicity with several compounds (3k, 3l) were found to be 12- to 77-fold more cytotoxic than SAHA. Docking experiments indicated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA. Our present results demonstrate that these novel hydroxamic acids are potential for further development as anticancer agents.

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Acknowledgements

We acknowledge the principal financial supports from the National Foundation for Science and Technology of Vietnam (NAFOSTED, Grant Number 104.01-2015.08). This work was also partly supported by the Grant Number 104.01-2014.55 (from NAFOSTED), the Korean Medical Research Center program (Grant Number 2008-0062275), and a small Grant from Hanoi University of Pharmacy.

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Authors and Affiliations

  1. Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Vietnam

    Tran Thi Lan Huong, Le Van Cuong, Pham Thu Huong, Tran Phuong Thao, Phan Thi Phuong Dung, Dao Thi Kim Oanh, Nguyen Thi Mai Huong, Hoang-Van Quan, Pham-The Hai & Nguyen-Hai Nam

  2. School of Medicine and Pharmacy, Hanoi National University, Hanoi, Vietnam

    Le-Thi-Thu Huong

  3. School of Chemical Engineering, Hanoi University of Science and Technology, 1 Dai Co Viet, Hanoi, Vietnam

    Tran Khac Vu

  4. College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, 28160, Korea

    Jisung Kim, Jae-Hee Lee & Sang-Bae Han

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  1. Tran Thi Lan Huong
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Correspondence to Sang-Bae Han or Nguyen-Hai Nam.

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Huong, T.T.L., Van Cuong, L., Huong, P.T. et al. Exploration of some indole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents. Chem. Pap. 71, 1759–1769 (2017). https://doi.org/10.1007/s11696-017-0172-1

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