medicinal-chemistry-biosimilars-2019-keynote

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Der Pharmacia Sinica
ISSN: 0976-8688 Page 23
Medicinal Chemistry and Biosimilars
March 25-26, 2019 | Budapest, Hungary
Euroscicon Conference on
Medicinal Chemistry & Biosimilars 2019
Innovative and strategic materials against tumor to decrease sharply the
number of people died by tumors are desired eagerly. To innovate inmedical
technologies of diagnosis and cure for various kinds of cancers by novel
medicinal materials, i.e., sugar dendritic Gd-DTPA complex MRI contrast
agent(DEN-OH)andIER5/Cdc25Btargetednovelmoleculartargetedphospha
sugar antitumor agents (e.g., TBMPP) were prepared and evaluated in vitro
and in vivo methods, and then these novel medicinal materials were revealed
preclinically to have excellent characters against tumor cells. Sugar dendritic
Gd-DTPA complex (DEN-OH) was prepared by introduction of protected
sugar dendritic parts to diethylenetriamine pentaacetic acid (DTPA) ligand
followed by the successive complex formation with Gd (III) and hydrolysis.
The prepared DEN-OH for MRI contrast agent (1/10 Gd concentration
compared with Magnevist) showed quite clearer images of quite early
stage of cancer (Figure 1). Phospha sugar derivatives, one of pseudosugar
derivatives (Figure 2), were prepared via traditional or newly developed
synthetic pathway to construct the compound library. Deoxybromophospha
sugar derivatives (e.g., TBMPP) prepared from phospholenes were first
found to exert quite effective and wide spectral antitumor activities by in vitro
evaluation against various kinds of leukemia cells such as K562 and U937
cell lines as well as solid cancer cells (stomac, lung, and skin cancers), where
normal cells were not suffered from any damages. Mechanistic studies of
phospha sugar (TBMPP) on leukemia cells by Western blotting showed that
the phospha sugar enhanced the expression of IER5, and then suppressed
the expression of Cdc25B in the cell cycle of tumor cells. As the results,
tumor cells might selectively and specifically might be induced apoptosis
at the mitosis step of the tumor cell cycle. In vivo evaluation for TBMPP was
successfully performed by using a nude mouse transplanted by K562 cells
on the skin (Figure 3)
Preclinical researches on tumor accumulative
novel sugar dendritic Gd-DTPA complex MRI
contrast agents and IER5/Cdc25B tageted novel
phospha sugar molecular trgeted antitumor
agents to innovate in cancer therapy
Biography
Mitsuji Yamashita has completed his PhD from
Nagoya University, Japan, and Postdoctoral studies
fromToyotaScienceandChemistryResearchCenter,
Japan, and Iowa State University, USA, as well as a
Visiting professor of University of Massachusetts,
USA, and a Visiting researcher of Oxford University,
UK. He was a Professor of Shizuoka University,
Japan, and he was retired at his age of 65 years
old followed by the university regulation. After the
retirement, he was a Special Professor and Guest
Professor of Shizuoka University. He is now a
Professor Emeritus of Shizuoka University and a part
time Lecturer of Shizuoka Science and Engineering
University, Japan, and established a private research
institute named “Research Institute for Innovative
and Strategic Materials of Medicinal Technology
against Tumors”. He has published more than 180
papers in journals and patents (more than 80 open
patents and 38 registered patents).
Mitsuji Yamashita et al., Der Pharmacia Sinica 2019, Volume:10
DOI: 10.21767/0976-8688-C1-001
Mitsuji Yamashita1, Hiroko Hasegawa1, Kazutaka Hirakawa 1, Reiko Makita1, Michio
Fujie2 , Satoki Nakamura2, Tatsuo Oshikawa3, Junko Yamashita1, Mitsuo Toda1,
Kazunori Ohnishi2, Haruhiko Sugimura2, Sophie Laurent 4 and Robert N Muller4
1 Shizuoka University, Japan, 2 Hamamatsu University School of Medicine, Japan
3 Numazu National College of Technology, Japan, 4University of Mons, BE