Enediynes Bearing Polyfluoroaryl Sulfoxide as New Antiproliferative Agents with Dual Targeting of Microtubules and DNA

Cyril Borie (1) , Shovan Mondal (2) , Tanzeel Arif (1) , Manon Briand (1) , Hugo Lingua (1) , Frederic Dumur (1) , Didier Gigmes (1) , Pierre Stocker (1) , Bernadette Barbarat (3) , Viviane Robert (4) , Cendrine Nicoletti (4) , Daniel Olive (5) , Marc Maresca (4) , Malek Nechab (1)

1 ICR - Institut de Chimie Radicalaire
2 Syamsundar College
3 IPC - Institut Paoli-Calmettes
4 ISM2 - Institut des Sciences Moléculaires de Marseille
5 Laboratoire d'Immunologie des Tumeurs

A novel series of enediynes possessing pentafluorophenylsulfoxide have been developed. The innovative compounds possess antiproliferative activity against a broad panel of human cancer cells originating from breast, blood, lung, kidney, colon, prostate, pancreas or skin with IC 50 ranging from 0.6 to 3.4 µM. The antiproliferative activity of enediynes in darkness is associated to their ability to compromise microtubule network. In addition, exposure to UV leads to double-stranded DNA cleavage caused by the newly synthesized molecules reducing further their IC 50 in nanomolar range against human tumor cells, including chemo-resistant pancreatic cancer cells. Taken together, the examined data demonstrate that enediynes possessing pentafluorosulfoxide are promising molecules in the cancer therapy.

Mots clés: Enediynes; Anticancer; Microtubules; DNA cleavage; light activation

Domaines: Chimie thérapeutique

Cyril Borie, Shovan Mondal, Tanzeel Arif, Manon Briand, Hugo Lingua, et al.. Enediynes Bearing Polyfluoroaryl Sulfoxide as New Antiproliferative Agents with Dual Targeting of Microtubules and DNA. European Journal of Medicinal Chemistry, 2018, 148, pp.306-313. ⟨10.1016/j.ejmech.2018.02.030⟩. ⟨hal-01765802⟩