New potential antitumor compounds from the plant Aristolochia manshuriensis as inhibitors of the CDK2 enzyme

Hegde, Vinod R.; Borges, Scott; Patel, Mahesh; Das, Pradip R.; Wu, Bonnie; Gullo, Vincent P.; Chan, Tze‐Ming

doi:10.1016/j.bmcl.2010.01.018

Cited by 23 publications

(14 citation statements)

References 22 publications

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“…Molecular structures of the Compound A and B were taken from the published report [9] and drawn in “Symyx Draw 4.0” program. Files were saved as MOLfile (*.mol).…”

Section: Methodsmentioning

confidence: 99%

“…Both compounds are composed of phenanthrene ring skeleton fused with a γ- lactame ring. Compound A has a hydroxy group (-OH) at C3 and C6 position and methoxy group (-OCH3) at C4 position [9]. This compound is closely related to Aristolactam AIIIa.…”

Section: Introductionmentioning

confidence: 99%

“…Dissimilar to compound A, position C3 and C4 of phenetherene ring is occupied by a dioxol (3, 4-dioxol) moiety in compound B. Compounds A and B were found to be active in the CDK2 enzyme inhibition assay, with IC50values of 140 nM and >10 µM, respectively interestingly, compound B showed more selectivity against other kinases like CDK4, aurora-2 kinase and MAP-kinase [9]. …”

Section: Introductionmentioning

confidence: 99%

“…Extensive X-ray crystallographic studies on complexes of the above listed inhibiters had elucidated the key features of interaction responsible for their affinity toward CDK2 protein. In this present in silico study we selected two newly isolated arisolactams from Aristolochia manshuriensis , which have been claimed to be a potent inhibitor of CDK2 and probably a lead for the development of anticancer drugs [9]. We studied and proposed structural basis of interaction of these two molecules with binding site of olomoucine on CDK2 protein (PDB ID 1W0X).…”

Section: Introductionmentioning

confidence: 99%

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Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors

Alshatwi¹,

Hasan²,

Syed³

et al. 2011

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Volume 7(7)ISSN Abstract:Aristolochia manshuriensis has been used for centuries in Chinese medicinal system for their versatile medicinal uses. Recent studies have revealed two new aristolactames (compound A and B) with γ-lactame ring fused with the phenentherene ring as potent inhibitors of human Cycline Dependent Kinase2 (CDK2). Studies on aristolactames and related compounds claim for their CDK2 inhibition without delineating the involved mechanism and structural basis of interaction. Molecular structural model was used to we propose a structural basis of CDK2 inhibition. We showed that these compounds (A and B) can successfully dock into the inhibitor binding pockets of human CDK2. Predicted binding affinities are comparable to known inhibitors of CDK2. Results were in agreement with the earlier biochemical studies. Hence, suggest that studied compounds A and B can be a promising scaffold for rational design of novel and potential drugs against cancer.

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“…Molecular structures of the Compound A and B were taken from the published report [9] and drawn in “Symyx Draw 4.0” program. Files were saved as MOLfile (*.mol).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors

Alshatwi¹,

Hasan²,

Syed³

et al. 2011

Bioinformation

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“…To remove AAs, they fermented AMK with fungi and mushroom and obtained more than 50% reduction of AAs of Aristolochiae species [19, 20]. In addition, Chung et al [21] and Hegde et al [22] found that novel phenanthrene compounds, such as aristopyridinone A, aristololamide II, and SCH546909, isolated from AMK have anti-inflammatory and antitumor activities. However, there was little information on their roles in mutagenicity and clastogenicity of AMK per se .…”

Section: Introductionmentioning

confidence: 99%

In VitroandIn VivoGenotoxicity Assessment ofAristolochia manshuriensisKom.

Hwang

Kim

Cho

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Arisolochiae species plants containing aristolochic acids I and II (AA I and AA II) are well known to cause aristolochic acid nephropathy (AAN). Recently, there are various approaches to use AAs-containing herbs after the removal of their toxic factors. However, there is little information about genotoxicity of Arisolochiae manshuriensis Kom. (AMK) per se. To obtain safety information for AMK, its genotoxicity was evaluated in accordance with OECD guideline. To evaluate genotoxicity of AMK, we tested bacterial reverse mutation assay, chromosomal aberration test, and micronucleus test. Here, we also determined the amounts of AA I and II in AMK (2.85 ± 0.08 and 0.50 ± 0.02 mg/g extract, resp.). In bacterial reverse mutation assay, AMK dose-dependently increased revertant colony numbers in TA98, TA100 and TA1537 regardless of metabolic activation. AMK increased the incidence of chromosomal aberration in Chinese hamster ovary-K1 cells, but there was no statistically significant difference. The incidences of micronucleus in bone marrow erythrocyte were significantly increased in mice after oral administration of AMK (5000 mg/kg), comparing with those of vehicle group (P < 0.05). The results of three standard tests suggest that the genotoxicity of AMK is directly related to the AAs contents in AMK.

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Pharmacognostic standardization and machine learning–based investigations on Akebia quinata and Akebia trifoliata

Qiu

Shi

2023

Biomedical Chromatography

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Currently, Akebiae Caulis is being used in clinical practice, but there are few reseaches on its different varieties. To ensure the accuracy and effectiveness of clinical practice, this study distinguished the Akebia quinata (Thunb.) Decne. and Akebia trifoliata (Thunb.) Koidz, using organoleptic evaluation, microscopic observation, fluorescence reaction, physicochemical properties, thin‐layer chromatography, IR spectroscopy, HPLC, four machine learning models, and in vitro antioxidant methods. Analysis of the powders of these two varieties using optical microscopy revealed the presence of starch granules, cork cells, crystal fibers, scalariform vessels, and wood fibers. Scanning electron microscopy revealed the presence of scalariform vessels, pitted vessels, wood fibers, and calcium oxalate crystals. Several tissues, including the cork layer, fiber population, cortex, phloem, pith, xylem, and ray, were found in the transverse section. In addition, thin‐layer chromatography was used to identify two components: oleanolic acid and calceolarioside B; 11 common peaks were identified in 15 batches of SAQ and 5 batches of SAT by using HPLC. Support vector machine, BP neural networks, and GA‐bp neural networks were able to predict 100% accurately of the different origins of stem of Akebia quinate (Thunb.) Decne (SAQ) and Akebia trifoliata (Thunb.) Koidz (SAT). Extreme learning machine achieved a correct rate of 87.5%. Meanwhile, Fourier‐transform infrared spectroscopy fingerprint identified nine characteristic absorption peaks of the secondary metabolites of SAQ and SAT. 2,2‐Diphenyl‐1‐1‐picrylhydrazyl experiment revealed that the IC50 values of SAQ and SAT extracts were 155.49 and 128.75 μg/ml, respectively. For the 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) assay, the IC50 value of SAT extract was found to be 269.24 μg/ml, which was lower than that of SAQ extract (IC50 = 358.99 μg/ml). This study successfully used different methods to differentiate between A. quinata (Thunb.) Decne. and A. trifoliata (Thunb.) Koidz., to help decide on which type to use for clinical application.

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New potential antitumor compounds from the plant Aristolochia manshuriensis as inhibitors of the CDK2 enzyme

Cited by 23 publications

References 22 publications

Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors

Predicting the possibility of two newly isolated phenetheren ring containing compounds from Aristolochia manshuriensis as CDK2 inhibitors

In VitroandIn VivoGenotoxicity Assessment ofAristolochia manshuriensisKom.

Pharmacognostic standardization and machine learning–based investigations on Akebia quinata and Akebia trifoliata

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