Self-assembling Releasable Thiocolchicine-Diphenylbutenylaniline Conjugates

  • ACS Med Chem Lett. 2019 Jan 4;10(4):611-614. doi: 10.1021/acsmedchemlett.8b00605.
Gaia Fumagalli  1 ,  Laura Polito  2 ,  Eleonora Colombo  1 ,  Francesca Foschi  1 ,  Michael S Christodoulou  1 ,  Francesco Galeotti  3 ,  Dario Perdicchia  1 ,  Ivan Bassanini  4 ,  Sergio Riva  4 ,  Pierfausto Seneci  1 ,  Aída García-Argáez  5  6 ,  Lisa Dalla Via  5 ,  Daniele Passarella  1
Affiliations
  • 1. Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy.
  • 2. CNR-ISTM, Via G. Fantoli 16/15, 20138 Milano, Italy.
  • 3. CNR-ISMAC, Via A. Corti 12, 20133 Milano, Italy.
  • 4. Istituto di Chimica del Riconoscimento Molecolare-C.N.R.-ICRM, Via Mario Bianco 9, 20131 Milano, Italy.
  • 5. Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via F. Marzolo 5, 35131 Padova, Italy.
  • 6. Fondazione per la Biologia e la Medicina della Rigenerazione T.E.S.-Tissue Engineering and Signalling Onlus, Via F. Marzolo 13, 35131 Padova, Italy.
PMID: 30996805 DOI: 10.1021/acsmedchemlett.8b00605
Abstract

The design and the synthesis of new self-assembling conjugates is reported. The target compounds are characterized by the presence of a self-immolative linker that secures a controlled release induced by Lipase cleavage. 4-(1,2-Diphenylbut-1-en-1-yl)aniline is used as a self-assembling inducer and amino-thiocolchicine as prototype of drug. The release of thiocolchicine derivative has been demonstrated in vitro in the presence of porcine pancreatic Lipase and Celite-supported Lipase. The formation of nanoparticles is confirmed by dynamic light scattering, atomic force microscopy, and fluorescence microscopy. The antiproliferative activity has been proved on two human Cancer cell lines.