Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents

Mopur Vijaya Bhaskar Reddy; Hsin-Yi Hung; Ping-Chung Kuo; Guan-Jhong Huang; Yu-Yi Chan; Shiow-Chyn Huang; Shwu-Jen Wu; Susan L Morris-Natschke; Kuo-Hsiung Lee; Tian-Shung Wu

doi:10.1016/j.bmcl.2017.02.038

Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents

Bioorg Med Chem Lett. 2017 Apr 1;27(7):1547-1550. doi: 10.1016/j.bmcl.2017.02.038. Epub 2017 Feb 20.

Authors

Affiliations

¹ Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan.
² School of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
³ School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan.
⁴ Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan.
⁵ Graduate Institute of Pharmaceutical Science, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan.
⁶ Department of Medical Technology, Chung Hua University of Medical Technology, Tainan 717, Taiwan.
⁷ Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
⁸ Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States; Chinese Medicinal Research and Development Center, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. Electronic address: khlee@unc.edu.
⁹ School of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung 907, Taiwan. Electronic address: tswu@mail.ncku.edu.tw.

PMID: 28256373
DOI: 10.1016/j.bmcl.2017.02.038

Abstract

Twenty-one chalcones were prepared via aldol condensation and subsequent reduction of these compound led to the corresponding dihydrochalcone and 1,3-diphenylpropane derivatives. The synthetic products were examined for their effects on NO inhibition in LPS-activated mouse peritoneal macrophages. Among the tested compounds, a 1,3-diarylpropane analog, 2-(3-(3,4-dimethoxyphenyl)propyl)-5-methoxyphenol (3p), displayed the most significant inhibitory effects against NO production. To investigate the mechanism of action, the effects of 3p on iNOS and COX-2 protein expression were studied by immunoblot. The results concluded that 3p is capable of inhibiting iNOS expression in LPS-induced RAW264.7 cells via attenuation of NF-κB signaling by ERK, p38, and JNK.

Keywords: 1,3-Diarylpropane analogs; Anti-inflammatory agents; Chalcones; Dihydrochalcones.

Publication types

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

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Cell Line
Chalcones / chemical synthesis
Chalcones / pharmacology*
Cyclooxygenase 2 / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism
JNK Mitogen-Activated Protein Kinases / metabolism
Mice
NF-kappa B / metabolism
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / metabolism
Phenols / chemical synthesis
Phenols / pharmacology*
Phosphorylation
Propane / analogs & derivatives*
Propane / chemical synthesis
Propane / pharmacology*
Signal Transduction
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

2-(3-(3,4-dimethoxyphenyl)propyl)-5-methoxyphenol
Anti-Inflammatory Agents, Non-Steroidal
Chalcones
NF-kappa B
Phenols
Nitric Oxide
Nitric Oxide Synthase Type II
Nos2 protein, mouse
Ptgs2 protein, mouse
Cyclooxygenase 2
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Propane