We design metal-complexes as mimics of antioxidant metalloenzymes (catalases, superoxide dismutases), to be used to rescue cells from oxidative stress. We study them in cellular models of oxidative stress. Some are low molecular weight complexes directly bio-inspired from superoxide dismutase. We have been playing with chemical design, notably modulating metal-complexes inertia to improve stability in the cell environment. We use analytical techniques in cells and cell lysates to characterize the speciation and metal exchange, the redox effect in cells as well as mitigation of the oxidative stress effect.

In a second strategy, we develop a combinatorial approach to design peptide-based complexes screened for their antioxidant activity. This methodology can be further extended to other types of activities. We have a strong focus on inflammatory bowel diseases.

We also develop Pt-based complexes for their anticancer activity, possibly in association with SOD mimics in the context of the reduction of anti-cancer drugs side effects, such as oxaliplatin with an efficient mitigation of peripheral neuropathy.

In a continuous search to transpose the metal complexes we develop to advanced systems, new delivery approaches are explored, including micelles or bacteria.

Collaborators:

• R. Lobinski, IPREM, Pau
• J. Vinh & G. Chiappetta, ESPCI-PSL, Paris
• P. Seksik & S. Demignot, CRSA, Paris
• G. Pastorin, NUS, Singapore
• G. Adriani, A*STAR Singapore
• W.K. Leong, NTU Singapore
• R. Coriat, Institut Cochin, Paris
• V. Pecoraro, U. Michigan, US
• M. L. Low, UCSI, Malaisie
• F. Gazeau, NABI, Paris
• F. Chain, L. Bermudez & P. Langella, Micalis, Jouy-en-Josas

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