In this study, the interaction between benzothiazole (BTA, concentration of a drug required for 50% inhibition in vitro (IC50) = 0.77 mM) and benzimidazole (BIA, IC50 = 2.14 mM) with urease was quantitatively assessed, using UV-Vis, molecular fluorescence, and circular dichroism. The results showed that both compounds interact with urease by a static fluorescence quenching mechanism with a non-fluorescent complex formation. The main forces responsible for stabilizing the supramolecular complex between BTA and urease were hydrophobic while, for BIA, van der Waals interactions and hydrogen bonds were the main ones. Urease conformation changes due to the interaction process were analyzed by circular dichroism and synchronous fluorescence. Besides, a competitive assay with substrate and inhibitors was used to evaluate the preferential urease site of interaction with BTA and BIA. Our experimental and theoretical studies supported that both, BTA and BIA, are mixed-inhibitors of ureases with a slight preference to the active site of such enzymes. Finally, both BTA and BIA showed to possess anti-Helicobacter pylori (one reference strain and six clinical isolates) activity, presenting minimal inhibitory concentration (MIC) values ranging from 38-150 and 20-164 µM, respectively. The urease inhibitors omeprazole and hydroxyurea showed MIC values in the range of 46-185 µM and 1683-> 3366 µM, respectively.

Four new complexes of formula [Fe(H2pcpa)2(H2O)2] (1), {[Mn(Hpcpa)(H2O)3]•1/2H2O}n (2), {[Zn(Hpcpa)(H2O)3]•1/2H2O}n (3) and [Cu2(Hpcpa)2(bipy)2]•8H2O (4) [H3pcpa = N-(4-carboxyphenyl)oxamic acid; bipy = 2,2¢-bipyridine] have been synthesized and their structures determined by X-ray diffraction. The structure of 1 consists of mononuclear iron(II) units where each iron(II) ion is six-coordinate by two trans-positioned water molecules and two bidentate H2pcpa- ligands building a distorted octahedral environment. 2 and 3 consist of neutral zigzag chains of MnII and ZnII ions respectively, the Hpcpa2- groups acting as linkers in a bidentate/monodentate coordination mode with three mer-positioned water molecules achieving the six-coordination around the metal centers. Compound 4 is a neutral centrosymmetric dicopper(II) complex where two Hpcpa2- groups adopting the bidentate/monodentate coordination mode and act as bridges and bidentate bipy molecules act as end-cap ligands, describing a square pyramidal surrounding around each copper atom. Cryomagnetic measurements for 1, 2 and 4 in the temperature range 1.9-300 K reveal the occurrence of a field-induced single-ion magnet (SIM) behavior (1) and weak interchain (J = -0.22 cm-1, 2) and intradimer (J = -0.39 cm-1, 4) antiferromagnetic interactions, the Hamiltonian being defined as H = -J Sa.Sb.

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.

O estudo do tautomerismo ceto-enólico e da estereoquímica de uma benzofenona natural com propriedades inibitórias sobre HIV, denominada (1R,5R,7R,8S)-(+)-3-(10-(3,4 -diidroxifenil)-10-hidroximetileno)-8-metil-1,5,7-tris(3-metil-2-butenil)-8-(4-metil-3-pentenil) -biciclo[3.3.1]nonano-2,4,9-triona (a), a qual foi isolada das sementes de Garcinia brasiliensis, é apresentado. A estrutura cristalina de (a), também conhecida como gutiferona A, foi determinada por difração de raios X e suas geometrias intra e intermolecular discutidas e comparadas com duas benzofenonas naturais análogas: clusianona and epiclusianona. Em (a), o átomo de hidrogênio hidroxílico proveniente do sistema ceto-enólico 2,4,10-triona está ligado ao átomo de oxigênio conectado ao grupo 10-(3,4-diidroxifenil)metileno, contrariamente ao verificado nas outras duas benzofenonas naturais similares, onde o átomo de hidrogênio equivalente está ligado em diferentes átomos de oxigênio pertencentes ao sistema anelar biciclo[3.3.1]nonano. Tal comportamento pode ser explicado pela presença do grupo OH6 no anel aromático que origina uma via ressonante deslocalizada adicional ao longo do sistema 3,4-diidroxifenil-C10-OH2. Em adição, a estereoquímica em torno do átomo C7 de (a) é comparada com as estruturas conhecidas da clusianona e da epiclusianona e a influência da configuração neste átomo de carbono quiral sobre as características estruturais encontradas no sistema ceto-enólico é proposta.

The keto-enol tautomerism and stereochemistry study of a HIV-inhibitory natural benzophenone, (1R,5R,7R,8S)-(+)-3-(10-(3,4-dihydroxyphenyl)-10-hydroxymethylene)-8-methyl -1,5,7-tris(3-methyl-2-butenyl)-8-(4-methyl-3-pentenyl)-bicyclo[3.3.1]nonane-2,4,9-trione (a), isolated from Garcinia brasiliensis seeds is presented. The crystal structure of (a), which is also know as guttiferona A, was determined by X-ray diffraction and its intra and inter-molecular geometries discussed and compared with two analogue natural benzophenones: clusianone and epiclusianone. In (a), the hydroxyl H atom from enolizable 2,4,10-trione moiety is linked in the oxygen atom bonded to 10-(3,4-dihydroxyphenyl)methylene group, in opposition to the related natural benzophenones, where this analogue H-atom is placed in different O-atoms from bicyclo[3.3.1]nonane ring system. Such behaviour can be explained by the presence of aromatic OH6 group in (a) that origins a further delocalized resonance path along of 3,4-dihydroxyphenyl-C10-OH2 group. In addition, the (a) stereochemistry around C7 atom is compared with known structures of clusianone and epiclusianone and the influence from configuration in this chiral C-atom to structural features found in the enolizable system is proposed.