@article{1dfbfcac99a847dbb5fb70aca10e6ca9,
title = "Design, synthesis and biological evaluation of 2-pyrrolone derivatives as radioprotectors",
abstract = "It is known that p53 is an important transcription factor and plays a central role in ionizing radiation (IR)-induced DNA damage responses such as cell cycle arrest, DNA repair and apoptosis. We previously reported that regulating p53 protein is an effective strategy for modulating cell fate by reducing the acute side effects of radiation therapy. Herein, we report on the discovery of STK160830 as a new radioprotector from a chemical library at The University of Tokyo and the design, synthesis and biological evaluation of its derivatives. The radioprotective activity of STK160830 itself and its derivatives that were synthesized in this work was evaluated using a leukemia cell line, MOLT-4 cells as a model of normal cells that express the p53 protein in a structure–activity relationships (SAR) study. The experimental results suggest that a direct relationship exists between the inhibitory effect of these STK160830 derivatives on the expression level of p53 and their radioprotective activity and that the suppression of p53 by STK160830 derivatives contribute to protecting MOLT-4 cells from apoptosis that is induced by exposure to radiation.",
keywords = "P53, Radiation therapy, Radioprotector",
author = "Hidetoshi Satoh and Shintaro Ochi and Kosuke Mizuno and Yutaka Saga and Shohei Ujita and Miyu Toyoda and Yuichi Nishiyama and Kasumi Tada and Yosuke Matsushita and Yuichi Deguchi and Keiji Suzuki and Yoshimasa Tanaka and Hiroshi Ueda and Toshiya Inaba and Yoshio Hosoi and Akinori Morita and Shin Aoki",
note = "Funding Information: This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (nos. 17K08225, 18F18412, and 20 K05712 for S.A.), a research grant from Uehara Memorial Foundation, a research grant from Tokyo Ohka Foundation for the Promotion of Science and Technology, Kanagawa, Japan, and a research grant from Tokyo Biochemical Research Foundation, Tokyo, Japan. We wish to acknowledge Fukiko Hasegawa and Dr. Yayoi Yoshimura (Faculty of Pharmaceutical Sciences, Tokyo University of Science) for collecting and interpreting the mass spectral data, Noriko Sawabe and Motoo Iida for the NMR measurements, and Hiroki Kuramochi (Research Institute for Science and Technology, Tokyo University of Science) for the elemental analyses. Funding Information: This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (nos. 17K08225, 18F18412, and 20 K05712 for S.A.), a research grant from Uehara Memorial Foundation, a research grant from Tokyo Ohka Foundation for the Promotion of Science and Technology, Kanagawa, Japan, and a research grant from Tokyo Biochemical Research Foundation, Tokyo, Japan. We wish to acknowledge Fukiko Hasegawa and Dr. Yayoi Yoshimura (Faculty of Pharmaceutical Sciences, Tokyo University of Science) for collecting and interpreting the mass spectral data, Noriko Sawabe and Motoo Iida for the NMR measurements, and Hiroki Kuramochi (Research Institute for Science and Technology, Tokyo University of Science) for the elemental analyses. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",
year = "2022",
month = aug,
day = "1",
doi = "10.1016/j.bmc.2022.116764",
language = "English",
volume = "67",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
}