Ohkura Kazuto, Tabata Atsushi, Uto Yoshihiro, Hori Hitoshi
Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan
Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan.
Anticancer Res. 2019 Aug;39(8):4479-4483. doi: 10.21873/anticanres.13622.
BACKGROUND/AIM: The stereo-configuration (R-, S-configuration) of chiral-2-nitroimidazole derivatives alters their radiosensitizing activity. This study aimed at examining the molecular features of these enantiomers by molecular simulation techniques.
A series of 2-nitroimidazole-based radiosensitizer TX-2036 molecules were synthesized, and their profiles were examined using molecular structural analysis such as conformation analysis, molecular orbital analysis, and electrostatic potential analysis.
R-configured TXs (TX-2043, -2030, -2036) had a weaker radiosensitizing activity than S-configured TXs (TX-2044, -2031, -2037), and R-compounds had a small minus electrostatic potential (ESP) field in the cyclopentene-1,3-dione region. S-configured TX-2046 had weaker radiosensitizing activity than R-configured TX-2045, and TX-2046 had a small minus ESP field as well as R-configured TX-2043, -2030, - 2036.
The cyclopentene-1,3-dione involved in the small minus ESP field affected the radiosensitizing activity of the TX-2036 series of molecules.
背景/目的：手性2-硝基咪唑衍生物的立体构型（R-、S-构型）会改变其放射增敏活性。本研究旨在通过分子模拟技术研究这些对映体的分子特征。
合成了一系列基于2-硝基咪唑的放射增敏剂TX-2036分子，并通过构象分析、分子轨道分析和静电势分析等分子结构分析方法对其特征进行了研究。
R构型的TXs（TX-2043、-2030、-2036）的放射增敏活性比S构型的TXs（TX-2044、-2031、-2037）弱，且R化合物在环戊烯-1,3-二酮区域有较小的负静电势（ESP）场。S构型的TX-2046的放射增敏活性比R构型的TX-2045弱，且TX-2046与R构型的TX-2043、-2030、-2036一样有较小的负ESP场。
参与较小负ESP场的环戊烯-1,3-二酮影响了TX-2036系列分子的放射增敏活性。
