Influence of side-chain changes on histone deacetylase inhibitory and cytotoxicity activities of curcuminoid derivatives

La-Or Somsakeesit; Thanaset Senawong; Pakit Kumboonma; Somprasong Saenglee; Arunta Samankul; Gulsiri Senawong; Chavi Yenjai; Chanokbhorn Phaosiri

doi:10.1016/j.bmcl.2020.127171

Influence of side-chain changes on histone deacetylase inhibitory and cytotoxicity activities of curcuminoid derivatives

Bioorg Med Chem Lett. 2020 Jun 1;30(11):127171. doi: 10.1016/j.bmcl.2020.127171. Epub 2020 Apr 4.

Authors

La-Or Somsakeesit¹, Thanaset Senawong², Pakit Kumboonma³, Somprasong Saenglee⁴, Arunta Samankul², Gulsiri Senawong², Chavi Yenjai¹, Chanokbhorn Phaosiri⁵

Affiliations

¹ Natural Products Research Unit, Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research and Innovation (Implementation Unit-IU, Khon Kaen University), Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand.
² Natural Products Research Unit, Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand.
³ Department of Applied Chemistry, Faculty of Science and Liberal Arts, Rajamangala University of Technology Isan, Nakhon Ratchasima 30000, Thailand.
⁴ Ban Dong Subdistrict Administration Organization, Ubolratana District, Khon Kaen 40250, Thailand.
⁵ Natural Products Research Unit, Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research and Innovation (Implementation Unit-IU, Khon Kaen University), Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: chapha@kku.ac.th.

PMID: 32273215
DOI: 10.1016/j.bmcl.2020.127171

Abstract

Using curcuminoids as lead compounds, fifty-nine curcuminoid derivatives with different side chains at the phenolic moiety were synthesized. All compounds were investigated for their histone deacetylase (HDAC) inhibitory activities. The potent pan-HDAC inhibitors were further tested against three human cancer cell lines including Hela, HCT116 and MCF-7 with MTT-based assay. The bisethylamide 4z and the mono-sec-butyl derivative 5j manifested good antiproliferative activities against HCT116 cancer cells with the IC₅₀ values as 14.60 ± 1.19 μg/mL and 7.33 ± 0.98 μg/mL, respectively. Molecular docking study of both compounds with Class I HDACs revealed that the compounds might bind tightly to the binding pocket of HDAC2. These findings suggested that these compounds can be putative candidates for the development of anticancer drugs via inhibiting HDACs.

Keywords: Anticancer; Curcumin; HDAC; Turmeric.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology
Binding Sites
Catalytic Domain
Cell Line, Tumor
Cell Proliferation / drug effects
Diarylheptanoids / analogs & derivatives*
Diarylheptanoids / metabolism
Diarylheptanoids / pharmacology
Histone Deacetylase Inhibitors / chemistry*
Histone Deacetylase Inhibitors / metabolism
Histone Deacetylases / chemistry*
Histone Deacetylases / metabolism
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Molecular Docking Simulation
Structure-Activity Relationship

Substances

Antineoplastic Agents
Diarylheptanoids
Histone Deacetylase Inhibitors
Isoenzymes
Histone Deacetylases