Design, synthesis and biological evaluation of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives as potent anticancer agents

Yang, Zhengmin; Huang, Jun; Qin, Jiang-Ke; Dai, Zhi-Kai; Lan, Wenli; Su, Gui‐Fa; Tang, Huang; Yang, Feng

doi:10.1016/j.ejmech.2014.07.076

Cited by 27 publications

(16 citation statements)

References 28 publications

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“…The basic active compound consists of a tricyclic planar bone with one pyran ring fused with two phenyl rings on both sides. 1 Natural xanthone compounds are reported to have various pharmacological activities, including antibacterial, 2 antivirus, 3 anthelmintics, 4 antiprotozoal, 5 hepatoprotective, 6 anti-inflammatory, 7 antimalarial, 8 antitrypanosomiasis, 9 and anticancer activities. Over the past decade, the anticancer activities of xanthone derivatives, mainly from natural origin, have been widely studied.…”

Section: Introductionmentioning

confidence: 99%

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Miladiyah

Jumina²,

Haryana³

et al. 2018

DDDT

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BackgroundXanthone derivatives have a wide range of pharmacological activities, such as those involving antibacterial, antiviral, antimalarial, anthelmintic, anti-inflammatory, antiprotozoal, and anticancer properties. Among these, we investigated the anticancer properties of xanthone. This research aimed to analyze the biological activity of ten novel xanthone derivatives, to investigate the most contributing-descriptors for their cytotoxic activities, and to examine the possible mechanism of actions of xanthone compound through molecular docking.Materials and methodsThe cytotoxic tests were carried out on WiDR and Vero cell lines, by a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay method. The structural features required for xanthone’s anticancer activity were conducted by using the semi-empirical Austin Model-1 method, and continued with quantitative structure-activity relationship (QSAR) analysis using BuildQSAR program. The study of the possible mechanism of actions of the selected xanthone compound was done through molecular docking with PLANTS.ResultsThe three novel xanthone derivatives (compounds 5, 7, and 8) exhibited cytotoxic activity with compound 5 showed the highest degree of cytotoxicity at concentration 9.23 µg/mL (37.8 µM). The following best equation model was obtained from the BuildQSAR calculation: log 1/IC50 = −8.124 qC1 −35.088 qC2 −6.008 qC3 + 1.831 u + 0.540 logP −9.115 (n = 10, r = 0.976, s = 0.144, F = 15.920, Q2 = 0.651, SPRESS = 0.390). This equation model generated 15 proposed new xanthone compounds with better-predicted anticancer activities. A molecular docking study of compound 5 showed that xanthone formed binding interactions with some receptors involved in cancer pathology, including telomerase, tumor-promoting inflammation (COX-2), and cyclin-dependent kinase-2 (CDK2) inhibitor.ConclusionThe results suggested that compound 5 showed the best cytotoxic activity among the xanthone derivatives tested. QSAR analysis showed that the descriptors contributed to xanthone’s cytotoxic activity were the net atomic charge at qC1, qC2, and qC3 positions, also dipole moment and logP. Compound 5 was suspected to be cytotoxic by its inhibition of telomerase, COX-2, and CDK2 receptors.

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Section: Introductionmentioning

confidence: 99%

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Miladiyah

Jumina²,

Haryana³

et al. 2018

DDDT

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“…In 2002, Moreau et al have been reported the synthesis of 2-arylhydrazonomethyl)substituted xanthones as antimycotics using Eaton's reagents [25]. The second study was the synthesis of 1-hydroxyl-3-aminoalkoxy xanthone as anticancer agent [26]. The last was reported in 2017 by Syahri et al [27], aiming to synthesize a series of hydroxyxanthone as antimalarial medication.…”

Section: Introductionmentioning

confidence: 99%

One-Pot Synthesis, Antioxidant Activity and Toxicity Evaluation of Some Hydroxyxanthones

Yuanita¹,

Pranowo²,

Siswanta³

et al. 2018

ChChT

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Some new hydroxyxanthone compounds were prepared through one pot cyclodehydration reaction of hydroxybenzoic acid derivatives (salicylic acid or resorcylic acid) with phloroglucinol or pyrogallol in the presence of Eaton's reagent (P 2 O 5 /MeSO 3 H). The synthesized compounds were screened for their antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods to determine their inhibitory concentration (IC 50). Cytotoxicity of the prepared compounds was also evaluated by MMT assay on Vero cell line. It was observed that the position and the number of hydroxyl groups could significantly affect the potent antioxidant activity of the prepared compounds. Cytotoxicity evaluation of new compounds indicated that the synthesized series of hydroxyl xanthone were categorized as very strong antioxidants and showed potential development as a commercial antioxidant compound.

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“…The structural diversity of xanthones is accompanied by their pleiotropic biological activity, which makes them potentially valuable, new therapeutic agents for the treatment of multiple disorders. The most significant activities of xanthones include anticancer [ 10 , 11 , 13 ], antibacterial, and antifungal activities [ 12 ]. Xanthones have significant effects in cardiovascular [ 14 ] and central nervous system diseases [ 15 ]; they also have immunomodulatory and anti-inflammatory potential [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Contribution of reactive oxygen species to the anticancer activity of aminoalkanol derivatives of xanthone

et al. 2017

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SummaryReactive oxygen species (ROS) are critically involved in the action of anticancer agents. In this study, we investigated the role of ROS in the anticancer mechanism of new aminoalkanol derivatives of xanthone. Most xanthones used in the study displayed significant pro-oxidant effects similar to those of gambogic acid, one of the most active anticancer xanthones. The pro-oxidant activity of our xanthones was shown both directly (by determination of ROS induction, effects on the levels of intracellular antioxidants, and expression of antioxidant enzymes) and indirectly by demonstrating that the overexpression of manganese superoxide dismutase decreases ROS-mediated cell senescence. We also observed that mitochondrial dysfunction and cellular apoptosis enhancement correlated with xanthone-induced oxidative stress. Finally, we showed that the use of the antioxidant N-acetyl-L-cysteine partly reversed these effects of aminoalkanol xanthones. Our results demonstrated that novel aminoalkanol xanthones mediated their anticancer activity primarily through ROS elevation and enhanced oxidative stress, which led to mitochondrial cell death stimulation; this mechanism was similar to the activity of gambogic acid.

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Design, synthesis and biological evaluation of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives as potent anticancer agents

Cited by 27 publications

References 28 publications

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

One-Pot Synthesis, Antioxidant Activity and Toxicity Evaluation of Some Hydroxyxanthones

Contribution of reactive oxygen species to the anticancer activity of aminoalkanol derivatives of xanthone

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Design, synthesis and biological evaluation of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives as potent anticancer agents

Cited by 27 publications

References 28 publications

Biological activity, quantitative structure&ndash;activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Biological activity, quantitative structure&ndash;activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

One-Pot Synthesis, Antioxidant Activity and Toxicity Evaluation of Some Hydroxyxanthones

Contribution of reactive oxygen species to the anticancer activity of aminoalkanol derivatives of xanthone

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Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs