Xanthenones were synthesized via one-pot tricomponent reaction, under solvent-free conditions, using aldehydes, phenolic and cyclic 1,3-dicarbonyl compounds. Natural organic acids (NOAs), compounds present in many living metabolisms, were used as potential green catalysts. NOA are considered to be more eco-friendly and user-friendly alternative to traditional methodologies. Optimization studies showed that oxalic acid was the best NOA catalyst for such reaction furnishing the xanthenones with up to 93% of yield. Theoretical calculations were performed to evaluate this reaction mechanism and regioselectivity. The results showed that the regiospecificity of this three-component reaction is kinetically and thermodynamically controlled by the addition of β-naphthol C2, instead of C10, to the aldehyde. Our results also disclosed two xanthenones as novel calcium channels blockers. Eco-friendly reaction conditions, easy workup procedure, short reaction times and good yields are some of the advantages of our methodology.

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.

Four sulfonamide-chalcone derivatives were prepared and their crystal structure were elucidated by single-crystal X-ray diffraction technique. They were synthesized by Claisen-Schmidt condensation reaction between N-(4-acetylphenyl)benzenesulfonamide or N-(4-acetylphenyl)-2,5-dichlorobenzenesulfonamide with benzaldehyde or p-nitrobenzaldehyde. Values of Z' > 1 are found in three compounds as a consequence of conformerism. The chalcone molecular backbones are featured by different levels of planarity in their conformers. Another conformational variability is in its benzenesulfonamide moiety. In the compound came from N-(4-acetylphenyl)benzenesulfonamide and benzaldehyde, there is a rotation of ca. 180° on the bond axis bridging the sulfonamide and chalcone motifs of one conformer if the two others are taken as references. The cytotoxic activity of all compounds synthesized here and of two other related sulfonamide chalcones was also assessed against three cancer cell lines (SF-295, HCT-8 and MDA-MB-435). The para-nitro compounds were the most active ones among all those tested, regardless of substitution pattern in benzenesulfonamide core.