Development of highly predictive 3D-QSAR CoMSIA models for anthraquinone and acridone derivatives as telomerase inhibitors targeting G-quadruplex DNA telomere

Zambre, Vishal P.; Murumkar, Prashant R.; Giridhar, Rajani; Yadav, Mange Ram

doi:10.1016/j.jmgm.2010.07.003

Cited by 26 publications

(4 citation statements)

References 39 publications

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“…AQ derivatives stabilize the G4 structure and further inhibit the function of telomerase. Here, a classical gel shift assay was combined with TRAP assay to investigate the telomerase inhibition ability of these AQ derivatives ( 32 , 35 , 36 ). Upon increasing the concentration of AQs, telomere DNA elongation was inhibited, as seen by the decreases in shifting bands (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth

et al. 2023

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Cyclic anthraquinone derivatives (cAQs), which link two side chains of 1,5-disubstituted anthraquinone as a threading DNA intercalator, have been developed as G-quartet (G4) DNA-specific ligands. Among the cAQs, cAQ-mBen linked through the 1,3-position of benzene had the strongest affinity for G4 recognition and stabilization in vitro and was confirmed to bind to the G4 structure in vivo, selectively inhibiting cancer cell proliferation in correlation with telomerase expression levels and triggering cell apoptosis. RNA-sequencing analysis further indicated that differentially expressed genes regulated by cAQ-mBen were profiled with more potential quadruplex-forming sequences. In the treatment of tumor-bearing mouse model, cAQ-mBen could effectively reduce tumor tissue and had less adverse effects on healthy tissue. These results suggest that cAQ-mBen can be a novel potential cancer therapeutic agent as a G4 binder.

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Section: Resultsmentioning

confidence: 99%

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth

et al. 2023

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“…Therefore, the discovery of novel therapeutic approaches is required to advance the treatment outcomes of patients with ER-negative breast cancer. Numerous studies have illustrated that the acridone nucleus, in addition to its derivatives, possess the property of a potent anticancer effect (10,11). However, the efficacy of acridone against human breast cancer is yet to be reported.…”

Section: Introductionmentioning

confidence: 99%

Acridone suppresses the proliferation of human breast cancer cells inï¿½vitro via ATP-binding cassette subfamily G member 2

Liu

et al. 2017

Oncol Lett

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Abstract. In the past decades, the tricyclic acridone ring system has become a focus of major research by medicinal chemists due to the biological significance of this moiety in drug design and discovery. Acridone has substantial bio-potential since it performs crucial functions, including antibacterial, antimalarial, antiviral and anti-neoplastic activities. However, the anticancer effect and the underlying mechanisms of acridone on breast cancer cells remains unclear. In the present study, the anti-tumor function and the underlying mechanisms of acridone were evaluated in vitro. Firstly, an MTT assay was used to evaluate the inhibitory effect of acridone. Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to investigate whether ATP binding cassette subfamily G member 2 (ABCG2) was associated with the function of acridone. Finally, western blotting was used to confirm the results of RT-qPCR. The present study demonstrated that acridone may decrease the proliferation of MDA-MB-231 cells dose-dependently. Further experiments revealed that acridone may downregulate the mRNA and protein expression levels of ABCG2, supporting the potential application of acridone in breast cancer treatment. These findings suggested that acridone is a potential agent in the treatment of human breast cancer.

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“…Three-dimensional quantitative structure-activity relationship (3D-QSAR) is one of the rational drug design approaches that is being successfully utilized for the development of potent bioactive compounds. Our laboratory has been actively engaged in designing potential enzyme inhibitors with the help of CADD techniques [21][22][23][24][25][26][27][28][29][30][31][32][33]. In this present work, we report a highly predictive 3D-QSAR model for peripherally acting selective CB1 receptor antagonists containing the 1,5-diaryl pyrazole scaffold.…”

Section: Introductionmentioning

confidence: 99%

Exploring structural requirements for peripherally acting 1,5-diaryl pyrazole-containing cannabinoid 1 receptor antagonists for the treatment of obesity

et al. 2015

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Peripherally acting cannabinoid 1 (CB1) receptor antagonists are considered as potential therapeutics for the treatment of obesity with desired efficacy and reduced central nervous system side effects. A dataset of 72 compounds containing the 1,5-diaryl pyrazole basic skeleton having peripheral CB1 receptor antagonistic activity was utilized for three-dimensional quantitative structure-activity relationship studies. Compounds of the series exhibited high variations in the biological activity and chemical structures. Different types of molecular alignments, such as atom-based, data-based, centroid-based and centroid/atom-based were utilized to develop the best CoMFA model. The best CoMFA model was obtained with a database alignment and the same alignment was further used for the development of a CoMSIA model. The best developed CoMFA model had [Formula: see text] with six components, [Formula: see text] while the best developed CoMSIA model had [Formula: see text] with six components, [Formula: see text] and [Formula: see text] The predictive [Formula: see text] values of these two models showed test set predictions of 0.528 and 0.679 for the best CoMFA and CoMSIA models, respectively. Based on a higher [Formula: see text] value, the CoMSIA model was found to be the best one. The prediction accuracy and reliability of the best developed CoMSIA model have been validated using well-established methods. Using the inputs from the best CoMSIA contour maps, several novel highly selective peripherally acting CB1 receptor antagonists have been designed and reported herein.

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Development of highly predictive 3D-QSAR CoMSIA models for anthraquinone and acridone derivatives as telomerase inhibitors targeting G-quadruplex DNA telomere

Cited by 26 publications

References 39 publications

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth

Acridone suppresses the proliferation of human breast cancer cells inï¿½vitro via ATP-binding cassette subfamily G member 2

Exploring structural requirements for peripherally acting 1,5-diaryl pyrazole-containing cannabinoid 1 receptor antagonists for the treatment of obesity

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