Synthesis and structure elucidation of 1-(2,5/3,5-difluorophenyl)-3-(2,3/2,4/2,5/3,4-dimethoxyphenyl)-2-propen-1-ones as anticancer agents
MEDICINAL CHEMISTRY RESEARCH
Authors: Yamali, Cem; Ozgun, Dilan Ozmen; Gul, Halise Inci; Sakagami, Hiroshi; Kazaz, Cavit; Okudaira, Noriyuki
Abstract
The compounds titled 1-(2,5/3,5-difluorophenyl)-3-(2,3/2,4/2,5/3,4-dimethoxyphenyl)-2-propen-1-ones (1-8) were synthesized via Claisen-Schmidt condensation under basic condition. The chemical structure of the compounds were identified using several spectroscopic techniques such as H-1 nuclear magnetic resonance (NMR), C-13 NMR, F-19 NMR, DEPT 90, DEPT 135, COSY, HMBC, and HMQC. Cytotoxic activities of the compounds were investigated towards several human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma derived from tongue (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)]. Most of these compounds presented higher cytotoxicity than reference drug 5-fluorouracil while the compounds 7, [1-(3,5-difluorophenyl)-3-(2,5-dimethoxyphenyl)-2-propen-1-one)], and 2, [1-(2,5-difluorophenyl)-3-(2,4-dimethoxyphenyl)-2-propen-1-one], were presenting the best activity according to potency selectivity expression values. Type of cell death induced by compound 7 in both HSC-2 and Ca9-22 cells was investigated to understand mechanism of action of the compounds. The compound 7 produced cleaved products of PARP and caspase-3 were produced, suggesting the induction of apoptosis as a possible mechanism of action of the compounds characterized via activation of caspase-3 in both human oral squamous cell carcinomas.
GeneChip Expression Profiling Reveals the Alterations of Energy Metabolism Related Genes in Osteocytes under Large Gradient High Magnetic Fields
PLOS ONE
Authors: Wang, Yang; Chen, Zhi-Hao; Yin, Chun; Ma, Jian-Hua; Li, Di-Jie; Zhao, Fan; Sun, Yu-Long; Hu, Li-Fang; Shang, Peng; Qian, Ai-Rong
Abstract
The diamagnetic levitation as a novel ground-based model for simulating a reduced gravity environment has recently been applied in life science research. In this study a specially designed superconducting magnet with a large gradient high magnetic field (LG-HMF), which can provide three apparent gravity levels (mu-g, 1-g, and 2-g), was used to simulate a space-like gravity environment. Osteocyte, as the most important mechanosensor in bone, takes a pivotal position in mediating the mechano-induced bone remodeling. In this study, the effects of LG-HMF on gene expression profiling of osteocyte-like cell line MLO-Y4 were investigated by Affymetrix DNA microarray. LG-HMF affected osteocyte gene expression profiling. Differentially expressed genes (DEGs) and data mining were further analyzed by using bioinfomatic tools, such as DAVID, iReport. 12 energy metabolism related genes (PFKL, AK4, ALDOC, COX7A1, STC1, ADM, CA9, CA12, P4HA1, APLN, GPR35 and GPR84) were further confirmed by real-time PCR. An integrated gene interaction network of 12 DEGs was constructed. Bio-data mining showed that genes involved in glucose metabolic process and apoptosis changed notablly. Our results demostrated that LG-HMF affected the expression of energy metabolism related genes in osteocyte. The identification of sensitive genes to special environments may provide some potential targets for preventing and treating bone loss or osteoporosis.