1262893-98-0Relevant articles and documents
New chiral stationary phases for liquid chromatography based on small molecules: Development, enantioresolution evaluation and chiral recognition mechanisms
Phyo, Ye' Zaw,Teixeira, Joana,Tiritan, Maria Elizabeth,Cravo, Sara,Palmeira, Andreia,Gales, Luís,Silva, Artur M.S.,Pinto, Madalena M.M.,Kijjoa, Anake,Fernandes, Carla
, p. 81 - 97 (2019/11/28)
Recently, we reported the development of new chiral stationary phases (CSPs) for liquid chromatography (LC) based on chiral derivatives of xanthones (CDXs). Based on the most promising CDX selectors, 12 new CSPs were successfully prepared starting from suitable functionalized small molecules including xanthone and benzophenone derivatives. The chiral selectors comprising one, two, three, or four chiral moieties were covalently bonded to a chromatographic support and further packed into LC stainless-steel columns (150?×?2.1?mm I.D.). The enantioselective performance of the new CSPs was evaluated by LC using different classes of chiral compounds. Specificity for enantioseparation of some CDXs was observed in the evaluation of the new CSPs. Besides, assessment of chiral recognition mechanisms was performed by computational studies using molecular docking approach, which are in accordance with the chromatographic parameters. X-Ray analysis was used to establish a chiral selector 3D structure.
New chiral derivatives of xanthones: Synthesis and investigation of enantioselectivity as inhibitors of growth of human tumor cell lines
Fernandes, Carla,Masawang, Kamonporn,Tiritan, Maria Elizabeth,Sousa, Emília,De Lima, Virgínia,Afonso, Carlos,Bousbaa, Hassan,Sudprasert, Wanwisa,Pedro, Madalena,Pinto, Madalena M.
, p. 1049 - 1062 (2014/02/14)
A highly efficient and practical methodology for synthesis of new chiral derivatives of xanthones (CDXs) in enantiomerically pure form has been developed According to this approach, thirty CDXs (3-32) were synthesized by coupling a carboxyxanthone (1) and a carboxymethoxyxanthone (2) with both enantiomers of commercially available chiral building blocks, namely six amino alcohols, one amine and one amino ester The activation of the carboxylic acid group of the xanthonic scaffold was carried out with the coupling reagent O-(benzotriazol-1-yl)-N-N-N′-N′-tetramethyluronium tetrafluoroborate (TBTU), in the presence of a catalytic amount of TEA in anhydrous THF The coupling reactions with the chiral blocks were performed at room temperature with short reactions times, excellent yields (ranging from 94% to 99%), and very high enantiomeric excess The synthesized CDXs were evaluated for their effect on the in vitro growth of three human tumor cell lines, namely A375-C5 (melanoma), MCF-7 (breast adenocarcinoma), and NCI-H460 (non-small cell lung cancer) The most active compound was CDX 15 being active in all human tumor cell lines with values of GI50 of 32.15 ± 2.03 μM for A375-C5, 22.55 ± 1.99 μM for MCF-7, and 14.05 ± 1.82 μM for NCI-H460 Nevertheless, some CDXs showed cell-type selectivity Furthermore, the growth inhibitory effects, in some cases, demonstrated to be depending on the stereochemistry of the CDXs An interesting example was observed with the enantiomers 3 and 4, which demonstrated high enantioselectivity for MCF-7 and NCI-H460 cell lines It can be inferred that the effects on the growth of the human tumor cell lines can be ascribed not only to the nature and positions of substituents on the xanthonic scaffold but also to the stereochemistry of the CDXs Some considerations regarding structure-activity relationship within this class of compounds will be highlighted
Synthesis of new chiral xanthone derivatives acting as nerve conduction blockers in the rat sciatic nerve
Fernandes, Carla,Pinto, Madalena M.,Tiritan, Maria Elizabeth,Oliveira, Laura,Leitao, Luis,Pozzi, Angelo,Noronha-Matos, Jose Bernardo,Correia-De-Sa, Paulo
, p. 1 - 11,11 (2020/07/31)
The synthesis and structure elucidation of three new chiral xanthone (9H-xanthon-9-one) derivatives (2-4) are fully reported. The coupling reactions of the synthesized building block 6-methoxy-9-oxo-9H-xanthene-2-carboxylic acid (1) with two enantiomerically pure amino alcohols ((S)-(+)-valinol and (S)-(+)-leucinol) and one amine ((S)-(-)-α-4-dimethylbenzylamine), were carried out using the coupling reagent O-(benzotriazol-1-yl-)-N,N,N′, N′-tetramethylluronium tetrafluoroborate (TBTU). The coupling reactions were performed with yields higher than 97% and enantiomeric excess higher than 99%. The structures of the compounds were established by IR, MS, and NMR ( 1H, 13C, HSQC, and HMBC) techniques. Taking into account that these new chiral xanthone derivatives have molecular moieties structurally very similar to local anaesthetics, the ability to block compound action potentials (CAP) at the isolated rat sciatic nerve was also investigated. Nerve conduction blockade might result from a selective interference with Na + ionic currents or from a non-selective modification of membrane stabilizing properties. Thus, the mechanism, by which the three chiral xanthone derivatives cause conduction blockade in the rat sciatic nerve and their ability to prevent hypotonic haemolysis, given that erythrocytes are non-excitable cells devoid of voltage-gated Na+ channels, are also described. Data suggest that nerve conduction blockade caused by newly-synthesized xanthone derivatives might result predominantly from an action on Na+ ionic currents. This effect can be dissociated from their ability to stabilize cell membranes, which became apparent only upon increasing the concentration of compounds 2-4 to the higher micromolar range.
