2. Academic Validation
  3. Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent

Synthesis, 3D-structure and stability analyses of NRPa-308, a new promising anti-cancer agent

  • Bioorg Med Chem Lett. 2019 Dec 15;29(24):126710. doi: 10.1016/j.bmcl.2019.126710.
Etienne Brachet 1,  Aurore Dumond 2,  Wang-Qing Liu 3,  Marie Fabre 4,  Mohamed Selkti 1,  Françoise Raynaud 5,  Olivier Hermine 6,  Rachid Benhida 7,  Philippe Belmont 1,  Christiane Garbay 5,  Yves Lepelletier 6,  Cyril Ronco 4,  Gilles Pagès 8,  Luc Demange 9
Affiliations

Affiliations

  • 1 Université de Paris, CiTCoM, UMR 8038 CNRS, Faculté de Pharmacie, F-75006 Paris, France.
  • 2 Centre Scientifique de Monaco, Biomedical Department, 8 quai Antoine Ier, MC-98000, Monaco.
  • 3 Université de Paris, CiTCoM, UMR 8038 CNRS & U 1268 INSERM, Faculté de Pharmacie, F-75006 Paris, France; Université de Paris, LCBPT, UMR 8601 CNRS, UFR Biomédicale des Saints-Pères, F-75006 Paris, France.
  • 4 Université Côte d'Azur, ICN, UMR 7272 CNRS, F-06108 Nice, France.
  • 5 Université de Paris, LCBPT, UMR 8601 CNRS, UFR Biomédicale des Saints-Pères, F-75006 Paris, France.
  • 6 INSERM UMR 1163, Laboratory of Cellular and Molecular Basis of Normal Hematopoiesis and Hematological Disorders: Therapeutical Implications, 24 boulevard Montparnasse, F-75015 Paris, France; Université de Paris, Imagine Institute, 24 boulevard Montparnasse, F-75015 Paris, France; CNRS ERL 8254, 24 boulevard Montparnasse, F-75015 Paris, France.
  • 7 Université Côte d'Azur, ICN, UMR 7272 CNRS, F-06108 Nice, France; Mohamed VI Polytechnic University, UM6P, 43150 BenGuerir, Morocco.
  • 8 Centre Scientifique de Monaco, Biomedical Department, 8 quai Antoine Ier, MC-98000, Monaco; Université Côte d'Azur, UMR 7284 CNRS and INSERM U 1081, Institute for Research on Cancer and Aging (IRCAN), Centre Antoine Lacassagne, 33 Avenue de Valombrose, F- 06189 Nice, France.
  • 9 Université de Paris, CiTCoM, UMR 8038 CNRS, Faculté de Pharmacie, F-75006 Paris, France. Electronic address: luc.demange@parisdescartes.fr.
PMID: 31699610 DOI: 10.1016/j.bmcl.2019.126710
Abstract

We report herein the synthesis of a newly described anti-cancer agent, NRPa-308. This compound antagonizes Neuropilin-1, a multi-partners transmembrane receptor overexpressed in numerous tumors, and thereby validated as promising target in oncology. The preparation of NRPa-308 proved challenging because of the orthogonality of the amide and sulphonamide bonds formation. Nevertheless, we succeeded a gram scale synthesis, according to an expeditious three steps route, without intermediate purification. This latter point is of utmost interest in reducing the ecologic impact and production costs in the perspective of further scale-up processes. The purity of NRPa-308 has been attested by means of conventional structural analyses and its crystallisation allowed a structural assessment by X-Ray diffraction. We also reported the remarkable chemical stability of this molecule in acidic, neutral and basic aqueous media. Eventually, we observed for the first time the accumulation of NRPa-308 in two types of human breast Cancer cells MDA-MB231 and BT549.

Keywords

Anti-cancer agents; NRP-a308 stability; NRPa-308 synthesis; Neuropilins.

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