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E u r o p e a n C o n g r e s s o n
Advanced Chemistry
Journal of Organic & Inorganic Chemistry
ISSN: 2472-1123
J u l y 1 2 - 1 3 , 2 0 1 8
P a r i s , F r a n c e
Advanced Chemistry 2018
Page 21
Flavaglines are a family of anticancer natural products that relieve the resistance
to cancer chemotherapies and display a strong cytotoxicity that is specific to
cancer identified thefirst synthetic flavaglines that inhibit cell proliferation
and viability (IC50≈1 nM) at lower doses than did the parent natural compounds. A
ligand for affinity chromatography was synthesized based on our structure affinity
relationship (SAR) information, and used for the identification of prohibitins-1 and
-2 as the molecular targets. Prohibitin-1 (PHB1) and its homologue prohibitin-2
(PHB2) are pleiotropic proteins that act as a hub for many signalling pathways.
We demonstrated that the binding of flavaglines to PHBs prevents the interaction
between PHBs and C-RAF and, thereby, inhibits C-RAF activation and subsequently
C-RAF-MEK-ERK signalling, which is critical to survival and proliferation of cancer
cells. With our collaborators, we found that another PHB ligand, fluorizoline, also
block C-RAF activation. Despite decades of research effort, clinically effective
medicines targeting C-RAF and KRAS remain elusive. Our recent results open
a novel avenue to inhibit both C-RAF and KRAS signalling with PHB ligands. We
also demonstrated that these compounds protect the heart from the adverse
effects of cancer chemotherapies involving anthracyclines. We showed that
this cardioprotection is mediated by the activation of the mitochondrial PHB-
STAT3 complex. In addition to these lines of research, we also developed new
PHB ligands belonging to the class of triazines that modulate the biosynthesis
of melanin in melanocytes and induce the death of cancer cells. The structure-
activity relationships of these new drugs and their detailed mechanism of action
will also be presented.
Biography
L Desaubry is a CNRS Research Director in the University of
Strasbourg in France (website:
and Adjunct Professor at Tianjin University of Science and
Technology (TUST) in China. In 1992, he received a PhD degree
in Medicinal Chemistry from Strasbourg University. Next, he
worked as a Post-doctoral fellow at SUNY at Stony Brook, USA.
He has completed Post-doctoral internship in Prof Pierre Cham-
bon’s laboratory previously to get a CNRS Research Senior Sci-
entist at the University of Strasbourg-CNRS. He was promoted
CNRS Research Director (corresponds to full professor) in 2014,
and also became professor at TUST in 2015. He has published
more than 70 publications and has been serving as an Editorial
Board Member of Frontiers in Chemistry, Medicinal Chemistry,
Advances in Oncology Research and Treatments and The Open
Medicinal Chemistry Journal.
Development of prohibitin ligands to
treat cancers, cardiac and immunological
disorders
L Desaubry1,2,4, H Abou-Hamdan1,2, Djehal1,3,
R Tabti1,2, S Elderwish1,2, N Chouha A 1 E Bentou-
hami1,3, Q Zhao1, D Wang4 , P Yu4 and C G Nebigil2
1LIT, CNRS/University of Strasbourg, France
2Sorbonne University, Paris, France
3LCIMN Laboratory, University Ferhat Abbas Setif, Algeria
4Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry,
Tianjin University of Science and Technology, China
L Desaubry et al., J Org Inorg Chem 2018, Volume: 4
DOI: 10.21767/2472-1123-C2-004