Prenylated xanthones: antiproliferative effects and enhancement of the growth inhibitory action of 4-hydroxytamoxifen in estrogen receptor-positive breast cancer cell line

Paiva, Ana Mafalda; Sousa, Emı́lia; Camões, Ana; Nascimento, María Säo José; Pinto, Madalena

doi:10.1007/s00044-011-9562-z

Cited by 21 publications

(24 citation statements)

References 30 publications

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“…Prenylated xanthones 4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano [3,2-b]xanthone, 3, 4-bis-(3-methylbut-2-enyloxy)-xanthone, and 3-(3-methylbut-2-enyloxy)-4-hydroxy-xanthone were obtained as described elsewhere. 29 The synthesis of the following thioxanthone derivatives was performed according to described procedures: 32 1-((2-(phenylamino)ethyl)amino)-4-propoxythioxanthone, 1-((3,5-dimethoxyphenyl)amino)-4-hydroxythioxanthone, 1-((3,4-dimethoxybenzyl)amino)-4-propoxythioxanthone, 1-((3,4,5-trimethoxyphenyl)amino)-4-propoxythioxanthone, 1-(piperidin-1-yl)-4-propoxythioxanthone (9), 1-(2-(1H-benzimidazol-2-yl)ethanamine)-4-propoxythioxanthone, 1-((2-(1,3-benzodioxol-5-yl)ethyl)amino)-4-propoxythioxanthone, 1-((2-(diethylamino)ethyl)amino)-4-propoxythioxanthone (10), 1-methoxy-4-propoxythioxanthone (11), 1-(isobutylamino)-4-propoxythioxanthone, and 1-(isopropylamino)-4-propoxythioxanthone.…”

Section: Chemistrymentioning

confidence: 97%

Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-ResistantStaphylococcus aureus

Bessa

Palmeira

Gomes

et al. 2015

Microbial Drug Resistance

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The extensive use of antimicrobials is leaving medicine with few effective therapeutic options to treat many infections due to the fact that many organisms developed resistance to commonly used drugs. It is therefore pertinent to search not only for new antimicrobials but also for compounds able to restore or potentiate the activity of existing antibiotics. We have screened a library consisting of 40 (thio)xanthone derivatives for antibacterial activity and possible synergistic effects when used in combination with antibiotics. Nine out of the 40 compounds exhibited antibacterial activity against Gram-positive bacteria. Two xanthone derivatives, 1-formyl-4-hydroxy-3-methoxy (7), 2-formyl-3-hydroxy-4-methoxyxanthone (8) and the thioxanthone derivative 1-((2-(diethylamino)ethyl)amino)-4-propoxythioxanthone (10) and its hydrochloride form 13, showed activity against a methicillin-resistant Staphylococcus aureus (MRSA) isolate with minimum inhibitory concentration (MIC) values lower than 256 μg/ml. Thioxanthone 10 demonstrated antibacterial activity and also synergy when combined with ampicillin and oxacillin against MRSA. Additionally, thioxanthone 1-(piperidin-1-yl)-4-propoxythioxanthone (9), despite not having antibacterial activity presented remarkable synergy with oxacillin against MRSA; the MIC of tioxanthone 9 and oxacillin when both were in combination were 128 and 8 μg/ml, respectively. Thioxanthones 9 and 10 were also found to be synergistic when both were combined. Subsequently, docking simulations between thioxanthones 9 and 10 and the allosteric domain of penicillin-binding protein 2A (PBP2A) were undertaken in AutoDock Vina. Both compounds had the ability to bind with an allosteric domain of PBP2A, which may explain their synergy with oxacillin. These two thioxanthone derivatives with different profiles may be promising tools for restoring the activity of oxacillin against MRSA.

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Section: Chemistrymentioning

confidence: 97%

Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-ResistantStaphylococcus aureus

Bessa

Palmeira

Gomes

et al. 2015

Microbial Drug Resistance

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“…The biological activity of xanthones and their derivatives is based on their tricyclic scaffold but depends on the nature and position of the different substituents [2] . Since xanthones may play a role as anti-proliferative and pro-apoptotic agents [2] , [11] , [12] , [13] , [14] , several derivatives, including (thio)xanthone derivatives, have been synthesized and tested in human cancer cell lines [14] , [15] , but not in fungi. It is thus important to add data from different organisms to the current knowledge on the mechanism of action of xanthones.…”

Section: Introductionmentioning

confidence: 99%

Transcription profiling of the Neurospora crassa response to a group of synthetic (thio)xanthones and a natural acetophenone

et al. 2015

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Xanthones are a class of heterocyclic compounds characterized by a dibenzo-γ-pyrone nucleus. Analysis of their mode of action in cells, namely uncovering alterations in gene expression, is important because these compounds have potential therapeutic applications. Thus, we studied the transcriptional response of the filamentous fungus Neurospora crassa to a group of synthetic (thio)xanthone derivatives with antitumor activity using high throughput RNA sequencing. The induction of ABC transporters in N. crassa, particularly atrb and cdr4, is a common consequence of the treatment with xanthones. In addition, we found a group of genes repressed by all of the tested (thio)xanthone derivatives, that are evocative of genes downregulated during oxidative stress. The transcriptional response of N. crassa treated with an acetophenone isolated from the soil fungus Neosartorya siamensis shares some features with the (thio)xanthone-elicited gene expression profiles. Two of the (thio)xanthone derivatives and the N. siamensis-derived acetophenone inhibited the growth of N. crassa. Our work also provides framework datasets that may orientate future studies on the mechanisms of action of some groups of xanthones.

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“…Recently, a dihydropyranoxanthone, synthetized by some of us, 3,4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3,2-b]xanthen-6-one (1, Fig. 1), presented significant antiproliferative and apoptotic inducing effects (Paiva et al, 2012;Palmeira et al, 2010) in human tumor cell lines. Both ␣-mangostin (Leão et al, 2013a) and compound 1 (Leão et al, 2013b) were shown to be promising inhibitors of p53-MDM2 interaction, with compound 1 showing the highest inhibitory activity in a yeast target-based assay, mimicking the activity of known p53 activators.…”

Section: Introductionmentioning

confidence: 99%

Development of noncytotoxic PLGA nanoparticles to improve the effect of a new inhibitor of p53–MDM2 interaction

Paiva

Pinto

Teixeira

et al. 2013

International Journal of Pharmaceutics

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a b s t r a c tOne possible approach to overcome solubility complications and enhance the biological activity of drugs is their incorporation into drug delivery systems. Within this scope, several nanosphere and nanocapsule formulations of a new inhibitor of p53-MDM2 interaction (xanthone 1) were developed and their physicochemical properties analyzed. Through the investigation of the effect of several empty nanoparticles on the growth of MCF-7 cells, it was possible to observe that four out of five formulations were cytotoxic and that some correlations between the toxic potential of these polymeric nanoparticles and their properties/composition could be extrapolated. One empty formulation of nanocapsules developed by emulsification/solvent evaporation and containing PLGA, PVA and Mygliol ® 812 was found to be noncytotoxic to this cell line. The corresponding compound 1-loaded nanocapsules showed an incorporation efficiency of 77% and revealed to be more potent than the free drug against cell growth inhibition, which may be related to the enhancement in its intracellular delivery. In an integrative study, the intracellular uptake of nanocapsules was confirmed using fluorescent 6-coumarin and well as compound 1 release from nanocapsules. Overall, it was possible to enhance the effect of the hit inhibitor of p53-MDM2 interaction through the development of suitable noncytotoxic polymeric nanoparticles.

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Prenylated xanthones: antiproliferative effects and enhancement of the growth inhibitory action of 4-hydroxytamoxifen in estrogen receptor-positive breast cancer cell line

Cited by 21 publications

References 30 publications

Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-ResistantStaphylococcus aureus

Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-ResistantStaphylococcus aureus

Transcription profiling of the Neurospora crassa response to a group of synthetic (thio)xanthones and a natural acetophenone

Development of noncytotoxic PLGA nanoparticles to improve the effect of a new inhibitor of p53–MDM2 interaction

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