Coniferyl aldehyde (1) is previously reported as a potent inducer of heat shock factor 1 (HSF1). Here, we further examined the active pharmacophore of 1 for activation of HSF1 using the derivatives coniferyl alcohol (2), 4-hydroxy-3-methoxyphenylpropanal (3), and 4-hydroxy-3-methoxyphenylpropanol (4). Both 1 and 2 resulted in increased survival days after a lethal radiation (IR) dose. The decrease in bone marrow (BM) cellularity and Ki67-positive BM cells by IR was also significantly restored by 1 or 2 in mice. These results suggested that the vinyl moiety of 1 and 2 is necessary for inducing HSF1, which may be useful for developing small molecules for cytoprotection of normal cells against damage by cytotoxic drugs and radiation.
Bibliographical noteFunding Information:
This work was supported by grants (2015M2A2A7A 03044831 and 2017R1A2B2002327) of the National Research Foundation of Korea (NRF), funded by the Korean government (Ministry of Science, ICT & Future Planning).
Irradiation. Cells in 60 mm Petri dishes were exposed to γ-radiation (7 or 10 Gy as a single dose) generated by a 137Cs gamma-ray source (Elan 3000, Atomic Energy of Canada, Mississauga, Canada) at a dose rate of 3.81 Gy/min. Radiation workers annually received radiation safety management training provided by the Korea Foundation of Nuclear Safety (KoFONS).
© 2017 The American Chemical Society and American Society of Pharmacognosy.