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, Emı́lia; Lima, Virgínia de; Afonso, Carlos; Bousbaa, Hassan; Sudprasert, Wanwisa; Pedro, Madalena; Pinto, Madalena

doi:10.1016/j.bmc.2013.12.042

Cited by 42 publications

(77 citation statements)

References 45 publications

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“…The effect of CDXs previously obtained in our group [40,41] as inhibitors of membrane located enzymes that might be involved in inflammatory processes, namely COX-1 and COX-2, was evaluated. Three enantiomeric pairs of CDXs were chosen to study the inhibitory effect of both enantiomers of each pair face to biological targets in order to evaluate potency and enantioselectivity.…”

Section: Resultsmentioning

confidence: 99%

“…CDXs (Figure 1) were synthesized in enantiomerically pure form [40,41]. Briefly, a carboxyxanthone derivative, with the structure based on some bioactive xanthones from marine origin [31] was coupled with both enantiomers of commercially available chiral building blocks using O -(benzotriazol-1-yl)- N-N-N’-N’ -tetramethyluronium tetrafluoroborate as coupling reagent and a catalytic amount of triethylamine in tetrahydrofuran, at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Search of new bioactive CDXs and investigation of enantioselectivity on their biological activity have remained an area of interest of our group [40,41]. Recently, we described the synthesis of new CDXs in enantiomerically pure form, and some of them exhibited growth inhibitory effects on different tumor cell lines as well as enantioselectivity [40].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we described the synthesis of new CDXs in enantiomerically pure form, and some of them exhibited growth inhibitory effects on different tumor cell lines as well as enantioselectivity [40]. In this context, herein we described the evaluation of COX inhibition activity and protein binding affinity for three enantiomeric pairs of CDXs (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

et al. 2017

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Searching of new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties, particularly those with anti-inflammatory activity, has remained an area of interest of our group. Herein, we describe in silico studies and in vitro inhibitory assays of cyclooxygenases (COX-1 and COX-2) for different enantiomeric pairs of CDXs. The evaluation of the inhibitory activities was performed by using the COX Inhibitor Screening Assay Kit. Docking simulations between the small molecules (CDXs; known ligands and decoys) and the enzyme targets were undertaken with AutoDock Vina embedded in PyRx—Virtual Screening Tool software. All the CDXs evaluated exhibited COX-1 and COX-2 inhibition potential as predicted. Considering that the (S)-(−)-enantiomer of the nonsteroidal anti-inflammatory drug ketoprofen preferentially binds to albumin, resulting in lower free plasma concentration than (R)-(+)-enantiomer, protein binding affinity for CDXs was also evaluated by spectrofluorimetry as well as in in silico. For some CDXs enantioselectivity was observed.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

et al. 2017

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“…[17][18][19][20][21] Xanthones (9H-xanthen-9-ones) comprise an important class of oxygenated heterocycles. 25 Along with the synthesis of new chiral bioactive xanthone derivatives, 25,26 we have developed LC methods for the efficient enantioresolution and determination of their enantiomeric purity using different types of CSPs. pharmacological activities, depending on the nature/position of the substituents in the xanthone scaffold.…”

Section: Introductionmentioning

confidence: 99%

Resolution, determination of enantiomeric purity and chiral recognition mechanism of new xanthone derivatives on (S,S)‐whelk‐O1 stationary phase

et al. 2017

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The enantioresolution and determination of the enantiomeric purity of 32 new xanthone derivatives, synthesized in enantiomerically pure form, were investigated on (S,S)-Whelk-O1 chiral stationary phase (CSP). Enantioselectivity and resolution (α and R ) with values ranging from 1.41-6.25 and from 1.29-17.20, respectively, were achieved. The elution was in polar organic mode with acetonitrile/methanol (50:50 v/v) as mobile phase and, generally, the (R)-enantiomer was the first to elute. The enantiomeric excess (ee) for all synthesized xanthone derivatives was higher than 99%. All the enantiomeric pairs were enantioseparated, even those without an aromatic moiety linked to the stereogenic center. Computational studies for molecular docking were carried out to perform a qualitative analysis of the enantioresolution and to explore the chiral recognition mechanisms. The in silico results were consistent with the chromatographic parameters and elution orders. The interactions between the CSP and the xanthone derivatives involved in the chromatographic enantioseparation were elucidated.

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Chiral Pharmaceuticals

Tiritan

Ribeiro

Fernandes

et al. 2016

Kirk-Othmer Encyclopedia of Chemical Technology

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The implication of chirality in pharmaceuticals is briefly reviewed, presenting the basic concepts and the chiral recognition phenomenon in biological systems. The importance to recognize enantiomers of chiral pharmaceuticals, both in pharmacology and environmental fields, is emphasized and many examples were selected to demonstrate the significance of chirality in both areas. Methodologies to obtain single enantiomers and to control the enantiomeric fraction associated with enantioseparation of chiral pharmaceuticals are also discussed. Several enantioselective methods using liquid chromatography (LC) with chiral stationary phases (CSPs) in biomedical and environmental fields are presented. The most used CSPs, their advantages and drawbacks, are swiftly revised.

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New chiral derivatives of xanthones: Synthesis and investigation of enantioselectivity as inhibitors of growth of human tumor cell lines

Cited by 42 publications

References 45 publications

Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

Resolution, determination of enantiomeric purity and chiral recognition mechanism of new xanthone derivatives on (S,S)‐whelk‐O1 stationary phase

Chiral Pharmaceuticals

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