Article Dans Une Revue International Journal of Molecular Sciences Année : 2025

Bicyclic N,S-Acetals Containing Fused Cysteine-Amide System as New Heterocyclic Class Targeting Human Farnesyltransferase (FTase-h)

Résumé

We report in this contribution the synthesis and in vitro biological evaluation of a novel class of chiral thiazoloisoindolinone scaffolds as potent inhibitors against human farnesyltransferase (FTase-h). The targeted products, sulfides (4), sulfoxides (5,6), and sulfones (7), containing up to three points of diversification, were obtained in a short-step sequence starting from the available and cost-effective L-cysteine hydrochloride (1), which is the source of N and S atoms and the chiral pool, and α-carbonyl benzoic acids (2), which are isoindolinone precursors. Concisely, the key ester intermediates (1) provide (a) sulfide-amides (4) by solvent-free amidation, (b) sulfoxides (5,6) by selective S-oxidation using NaIO4, and (c) sulfones (7) by oxidation using MMPP. Finally, the obtained N,S-acetal systems have shown promising inhibitory activities on FTase-h in the nanomolar range with excellent half maximal inhibitory concentration (IC50) values up to 4.0 nanomolar (for example, 25.1 nM for sulfide 4bI, 67.3 nM for sulfone 7bG, and more interesting of 4.03 nM for sulfoxide 5bG).

Domaines

Fichier principal
Vignette du fichier
ijms-26-01717.pdf (22.59 Mo) Télécharger le fichier
Origine Publication financée par une institution
Licence

Dates et versions

hal-05025962 , version 1 (02-04-2026)

Licence

Identifiants

Citer

Fanny Danton, Mohamed Othman, Ata Martin Lawson, Amaury Farce, Emmanuelle Lipka, et al.. Bicyclic N,S-Acetals Containing Fused Cysteine-Amide System as New Heterocyclic Class Targeting Human Farnesyltransferase (FTase-h). International Journal of Molecular Sciences, 2025, 26 (4), pp.1717. ⟨10.3390/ijms26041717⟩. ⟨hal-05025962⟩
124 Consultations
8 Téléchargements

Altmetric

Partager

  • More