Defence of Marcel Annereau’s thesis (CHEMBIO group)

Friday 18th October 2024
at 2 pm

Pierre et Marie Curie Campus
Esclangon building
Amphitheater Durand

Marcel ANNEREAU, a doctoral student in the CHEMBIO group, will present his thesis entitled

« Development of new  liver cancer treatment strategies by using CO-releasing molecules (CORMs) »

Carbon monoxide (CO) is known in the popular culture as a lethal gas, earning its name of “silent killer”. Since the past decade, CO has emerged as a promising therapeutic agent for cancer treatment when administrated at optimal concentrations.1 However, due to its gaseous form, CO remains difficult to handle. To overcome this issue, Carbon Monoxide Releasing Molecules (CORMs) have been introduced as a more convenient mode of administration.2 These molecules are mostly organometallic complexes, enabling the release of CO upon a given external stimulus, such as visible light. These complexes, named photoCORMs, remain the most widely developed so far.3 Despite some recent advances, efforts are still ongoing to synthesize new carbonyl complexes combining light absorption in the visible region and high potency of vectorization for the site-selective, controlled delivery of CO.4 In this context, we present a new series of photo-activatable complexes [Mn(8-hydroxyquinoline)(CO)3(Imd)] with Imd = imidazole derivatives. We developed an expedite synthetic route from the dimeric structure [Mn2(8-HQ)2(CO)6] and applied a series of imidazole ligands (Fig. 1a). The use of various imidazole-based ancillary ligands allows the synthesis of a wide range of complexes with a high degree of modularity due to the presence of allyl, hydroxyl, or amine groups on the imidazole ring. Moreover, N,C-diprotected histidine was successfully applied, opening the way to further functionalization with peptides5 (Fig. 1b).

Finally, we successfully developed a series of new glycoconjugated CORM (GlycoCORMs) to allow targeted delivery of CO to cancer cells (Fig. 2). The first biological results showed an enhanced cytotoxicity for the GlycoCORMs compared to [Mn(8-HQ)(CO)3Me- Imd] with IC50 in the µM range, respectively 5 µM and 9 µM, assessing the positive role of the carbohydrate moiety in the biological activity of the glycoCORMs.

Find out more about the CHEMBIO group

Références:

  1. Y. Zhou, W. Yu, J. Cao, Biomaterials, 2020, 255,120193.
  2. R. Motterlini, J. E. Clark, R. Foresti, P. Sarathchandra, B. E. Mann, C. J. Green, Circ. Res., 2002, 90, E17-E24.
  3. R. Motterlini, L. E. Otterbein, Nat. Rev. Drug. Discov., 2010, 9, 453-460.
  4. C. C. Romão, W. A. Blättler, J. D. Seixas, G. J. Bernardes, Chem. Soc. Rev., 2012, 41, 3571-3583.
  5. M. Annereau, F. Martial, J. Forté, G. Gontard, S. Blanchard, H. Dossmann, M. Salmain and V. Corcé, Appl. Organomet. Chem., 2023, e7171