Study of Reactions of Two Mannich Bases Derived of 4’-Hydroxychalcones with Glutathione by RP‑TLC, RP‑HPLC and RP‑HPLC‑ESI‑MS Analysis

Abstract

4'-Hydroxychalcones have been reported to possess several beneficial biological effects. Several lines of evidence accumulated to demonstrate increased biological activities of the Mannich base derivatives of the parent 4'-hydroxychalcones. Bioactivities of chalcones and related α,β-unsaturated ketones are frequently associated with their reactivity with cellular thiols, such as GSH. For comparison of GSH reactivity, two bis Mannich bases of two 4'-hydroxychalcones were synthesized and reacted with GSH under non-cellular conditions. Reversed-phase thin layer chromatography (RP-TLC) and reversed-phase high performance liquid chromatography (RP-HPLC) analysis showed formation of two polar products which structures were confirmed by RP-HPLC-ESI-MS (RP-HPLC-electrospray ionization mass spectrometry) as 1:1 chalcone-GSH adducts in each case. At pH values below 8.0, the two bis Mannich bases showed higher GSH reactivity than two 4'-hydroxychalcones. Influence of the nature of the amino groups, the ring-B substituents and pH of the medium on reactivity was also investigated. The findings could serve as useful structure-activity information for subsequent molecular modification of thiol-reactive 4'-hydroxychalcones.

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

“…Furthermore, Mannich derivatives of hydroxychalcones have been reported to have increased anti‐inflammatory activity . In our previous communication synthesis and reaction of 4′‐hydroxychalcone 1 and its bis ‐Mannich derivative 2 (Figure ) with reduced GSH have been reported . Reaction of the investigated chalcones with GSH led to formation of two diastereomeric adducts in each case.…”

“…Under strong acid conditions (pH 3.2), the reaction rates were found to be significantly lower than those observed under more basic conditions (pH 6.1, pH 7.4, and pH 8.0). Furthermore, at each investigated pH, the rate of reaction of the bis ‐Mannich derivative 2 was found to be substantially higher than that of the parent (non‐Mannich) chalcone 1 …”

“…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 .…”

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“…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.…”