Synthesis and antitumor activities investigation of a C-nucleoside analogue of ribavirin

Eur J Med Chem. 2020 Feb 15:188:112009. doi: 10.1016/j.ejmech.2019.112009.

Nazarii Sabat ¹, Evelyne Migianu-Griffoni ², Tiffany Tudela ³, Marc Lecouvey ², Sabrina Kellouche ³, Franck Carreiras ³, Florian Gallier ¹, Jacques Uziel ¹, Nadège Lubin-Germain ⁴

Affiliations

1 Laboratoire de Chimie Biologique, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise, France.
2 Université; Paris 13, Sorbonne Paris Cité, Laboratoire de Chimie, Structure, Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), CNRS UMR 7244, 74, rue Marcel, Cachin, F-93017, Bobigny, France.
3 Equipe de Recherche sur les Relations Matrice Extracellulaire-Cellules, ERRMECe (EA1391), Institut des Matériaux, I-MAT (FD4122), University of Cergy-Pontoise, MIR, rue Descartes, 95031, Neuville sur Oise Cedex, France.
4 Laboratoire de Chimie Biologique, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise, France. Electronic address: [email protected].

PMID: 31883488 DOI: 10.1016/j.ejmech.2019.112009

Abstract

SRO-91 is a non-natural ribofuranosyl-1,2,3-triazole C-nucleoside obtained by a synthetic sequence involving a C-alkynyl glycosylation mediated by metallic indium and a Huisgen cycloaddition for the construction of the triazole. Its structure is close to the one of ribavirin, a drug presenting a broad-spectrum against viral infections. SRO-91 antitumor activities were investigated on 9 strains of tumor cells and IC₅₀ of the order of 1 μM were obtained on A431 epidermoid carcinoma cells and B16F10 skin melanoma cells. In addition, studies of ovarian tumor cell inhibitions show an interesting activity in regard to the need for new drugs for this pathology. Finally, cytotoxicity and mouse toxicity studies reveal a favorable therapeutic index for SRO-91.

Keywords

Antitumor activity; C-nucleoside; Ovarian cancer; Ribavirin.

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