New approaches in the design of Pt-based drugs: carrier molecules and photoactivation

J. P. Cerón-Carrasco
Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Science Department, Universidad Católica San Antonio de Murcia (UCAM), Murcia, Espagne
Vendredi 3 Mars 2017, 11h00
bibliothèque LCT, tour 12 - 13, 4^ème étage

Chemotherapy with platinum (i.e. cisplatin, carboplatin, nedaplatin and oxaliplatin) is now routinely used for cancer treatment [1]. Unfortunately, such compounds has critical side effects caused by the interaction of the metallic centre with both tumours and healthy tissues, which eventually limit their efficiency [2]. In this talk, we will review how one can use theoretical tools - including docking, molecular dynamics and density functional theory calculations - to help to design enhanced drugs, with a focus on carrier molecules. Indeed, this seminar will mainly touch up the application of Herceptin (Figure 1), an antibody that selectively recognises the Her2/neu over-expressed protein of breast cancer cells [3], as a drug-carrier molecule for metallodrugs. We finally discuss the required steps towards the synthesis of improved platinum(II)-based drugs beyond classical cisplatin derivatives.

[Picture]

Figure 1. Chemical structure of the novel platinum-based drug (LPtCl₂) and the chemical model built up to simulate the encapsulation of the drug into an antibody (Herceptin).

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Références :
[1] L. Kelland, Nat. Rev. Cancer 2007, 7, 573-584.
[2] M. A. Jakupec, M. Galanski, V. B. Arion, C. G. Hartinger, B. K. Keppler, Dalton Trans. 2008, 2, 183-194.
[3] H. S. Cho, K. Mason, K. X. Ramyar, A. M. Stanley, S. B. Gabelli, D. W. Denney Jr, D. J. Leahy, Nature 2003, 421, 756-760.