(E)-2-Benzylidenebenzocyclanones: Part VII. Investigation of the conjugation reaction of two cytotoxic cyclic chalcone analogues with glutathione: an HPLC–MS study

Abstract

The non-enzyme-catalyzed reaction of reduced glutathione (GSH) with two tumor cell cytotoxic cyclic chalcone analogues was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC). HPLC analysis of the reaction mixtures indicated the formation of two diastereomeric chalcone-GSH adducts in each case, whose structural assignments were supported by MALDI-TOF-MS and HPLC-MS with electrospray ionization (ESI) measurements. Such reactivity accounts for the previously observed effect of the two cyclic chalcone analogues on the in vivo cellular thiol level of Jurkat T cells.

Reagent‐induced asymmetric induction in addition reaction of reduced glutathione onto bis‐Mannich chalcones

“…In the case of flavones, Band I is associated with the cinnamoyl moiety while Band II with the benzoyl moiety of the compounds, both involving mainly –* electron transitions . Earlier it was demonstrated that addition of GSH onto the chalcone carbon–carbon double bond affects Band I but not Band II absorption . Accordingly, we monitored the compounds and their conjugates using the maximum ( λ = 254 nm) corresponding to the Band II absorption.…”

“…Several reports have been published demonstrating enhanced cancer cell cytotoxic activity of Mannich derivatives of hydroxychalcones in comparison to their non‐Mannich counterparts . Furthermore, Mannich derivatives of hydroxychalcones have been reported to have increased anti‐inflammatory activity .…”

Untitled

“…Reduced glutathione (GSH) is the most abundant cytosolic thiol playing important role in protection of cells against electrophiles-initiated damages [17]. Earlier we have demonstrated that chalcones (open-chain α,β-unsaturated carbonyls) [18] and cyclic chalcone analogues [19,20] possess intrinsic reactivity towards GSH resulting in formation of the expected adducts. Accordingly, thiol reactivity of α,β-unsaturated carbonyl compounds is a basis of one of the biotransformation pathways of this kind of xenobiotics.…”

(E)-2-Benzylidenecyclanones: Part XV. Stereochemistry of Reaction of 2-Arylidenecyclopentanones with Dithiocarbamic Acid

“…Reduced glutathione (GSH) is the most abundant cytosolic thiol playing important role in protection of cells against electrophilesinitiated damages. 17 Earlier we have demonstrated that chalcones (open-chain α,β-unsaturated carbonyls) 18 and cyclic chalcone analogues 19,20 possess intrinsic reactivity towards GSH resulting in formation of the expected adducts. Accordingly, thiol reactivity of α,β-unsaturated carbonyl compounds is a basis of one of the biotransformation pathways of this kind of xenobiotics.…”