Novel R3M (M = Si, Ge) substituted furan and thiophene-derived aldimines Synthesis, electrochemistry, and biological activity [Nouvelles aldimines dérivées du furanne et du thiophène substituées par R3M (M = Si, Ge) Synthèse, électrochimie et activité biologique]
Résumé
New furan and thiophene derivatives of aldimines o-HO-C6H4N[dbnd]CHC4H4X(R) (X = O, S; R = H, SiMe3, SiEt3, GeMe3, GeEt3) were synthesized by condensation of o-aminophenol with the substituted aldehyde precursor. Their structure, electrochemical reduction/oxidation (in CH3CN/0.1 M Bu4NPF6), frontier orbital energies, and cytotoxicity have been studied. Their electrochemical redox potentials Ep show good correlation with the corresponding orbital energies and the difference Ep ox – Ep red corresponds well to their orbital hardness. These new compounds have a pronounced cytotoxicity toward cancer cells of human fibrosarcoma HT-1080 and mouse hepatoma MG-22A (IC50 ≅ 1–8 μg ml−1) that can be modulated by introducing a Me3M substituent into the fifth position of the heterocycle (e.g., IC50(Me3Si)/IC50(H) ≥ 50). R3M-substitution reduces the orbital hardness of the aldimines studied and facilitates oxidation, promoting their oxidative metabolism. The neighboring group effect in the α-Me3Si-substituted thiophene derivative favors S-oxidation, which supposedly makes its metabolic mechanism different compared to R3M-substituted furan series (or for M = Ge in the thiophene series). Interestingly, SiMe3 and GeMe3 groups in both heterocyclic series (furan and thiophene) cause opposite trends in cytotoxicity, while the silyl group increases it, the germyl group decreases it. © 2019 Académie des sciences