Title of the thesis: Extraction and synthesis of new antiproliferative and anti-inflammatory Naphtoquinone derivatives
Supervisor : Pr Pierre Chalard
Laboratory : Institut de Chimie de Clermont-Ferrand
University : SIGMA Clermont
Email and Phone : [email protected]
Possible co-supervisor : Dr Isabelle Thomas
Laboratory : Instutut de Chimie de Clermont-Ferrand
University : SIGMA Clermont
Obesity is a risk factor for breast cancer in postmenopausal women, but also for recurrence and mortality. Overweight promotes resistance to treatment and is also associated with chronic inflammatory deases. Thus, the development of molecules with both antiproliferative and anti-inflammatory potential would be of great interest. In this context, one innovation pathway consist to isolate and to elucidate the structure of bioactive substances extracted from plants used in traditional pharmacopoeia, which constitute a great potential of secondary metabolites still uninvestigated.1 Following this strategy, in 2011, we have isolate a new naphtoquinone named Guieranone B, from a medicinal plant used for its analgesic activities, Guiera senegalensis, with remarkable antiproliferative activities on cell lines. MCF7 (breast cancer).2 In a synthetic approach of this molecule, we have prepared original naphthoquinones which have revealed a very good anti-proliferative activity. On the other hand, the anti-inflammatory activity of natural compounds of similar structures has recently been reported.3
The objective of our project will be to develop this new family of naphthoquinones and evaluate their anti-inflammatory and antiproliferative potential. This study will be carried out in close partnership with the ECREIN team (Professor Florence Cladefie-Chézet, UMR INRA-UCA 1019, Human Nutrition Unit).
1 Newman DJ, Cragg GM J. Nat. Prod. 2016, 79, 629-661 : “Natural products as sources of new drugs from 1981 to 2014”
2 Chalard P, Patel K, Caldefie-Chezet F, Delort L WO 2013 037964 (A1), “Anticancer Active Ingredient from Guiera senegalensis”
3 Zhanga Y, Wanga K, Chena H, Hea R, Caic R, Lid J, Zhoua D, Liua W , Huangc X, Yanga R, Denga S, Lia J, Guand X Phytochemistry 2018, 153, 36–47 : “Anti-inflammatory lignans and phenylethanoid glycosides from the root of Isodon ternifolius (D.Don) Kudô”
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