A mode of action study of cationic anthraquinone analogs: a new class of highly potent anticancer agents

Shrestha, Jaya P.; Subedi, Yagya Prasad; Chen, Liaohai Leo; Chang, Cheng‐Wei Tom

doi:10.1039/c5md00314h

Cited by 51 publications

(35 citation statements)

References 29 publications

(65 reference statements)

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“…For instance, Eltrombopag is used for thrombocytopenia, or low platelet count [61]. Additionally, Doxorubicin and Mitoxanthrone, possessing the Quinone substructure [62,63], are used as anticancer chemotherapy drugs [63].…”

Section: Resultsmentioning

confidence: 99%

Discorhabdin N, a South African Natural Compound, for Hsp72 and Hsc70 Allosteric Modulation: Combined Study of Molecular Modeling and Dynamic Residue Network Analysis

Amusengeri

Bishop

2019

Molecules

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The human heat shock proteins (Hsps), predominantly Hsp72 and Hsp90, have been strongly implicated in various critical stages of oncogenesis and progression of human cancers. While drug development has extensively focused on Hsp90 as a potential anticancer target, much less effort has been put against Hsp72. This work investigated the therapeutic potential of Hsp72 and its constitutive isoform, Hsc70, via in silico-based screening against the South African Natural Compounds Database (SANCDB). A comparative modeling approach was used to obtain nearly full-length 3D structures of the closed conformation of Hsp72 and Hsc70 proteins. Molecular docking of SANCDB compounds identified one potential allosteric modulator, Discorhabdin N, binding to the allosteric β substrate binding domain (SBDβ) back pocket, with good binding affinities in both cases. This allosteric region was identified in one of our previous studies. Subsequent all-atom molecular dynamics simulations and free energy calculations exhibited promising protein–ligand association characteristics, indicative of strong binding qualities. Further, we utilised dynamic residue network analysis (DRN) to highlight protein regions actively involved in cross-domain communication. Most residues identified agreed with known allosteric signal regulators from literature, and were further investigated for the purpose of deducing meaningful insights into the allosteric modulation properties of Discorhabdin N.

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Section: Resultsmentioning

confidence: 99%

Discorhabdin N, a South African Natural Compound, for Hsp72 and Hsc70 Allosteric Modulation: Combined Study of Molecular Modeling and Dynamic Residue Network Analysis

Amusengeri

Bishop

2019

Molecules

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“…The anthraquinones of A. vera are bioavailable and therapeutic and have been the subject of numerous studies on cancer and aging (Abdissa, et al, ; Lv, et al, ; Shrestha, Subedi, Chen, & Chang, ). These studies mostly focused on medical aspects such as antioxidant and anticancer properties, and few considered antiglycation activity (Lo, et al, ; Nemmar, et al, ).…”

Section: Resultsmentioning

confidence: 99%

Main anthraquinone components in Aloe vera and their inhibitory effects on the formation of advanced glycation end-products

Kang

Zhao

et al. 2016

Journal of Food Processing and Preservation

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Food heating process causes increased protein glycation and the formation of advanced glycation endproducts (AGEs) which related with diabetes and ageing. Aloe vera (A. vera) extract is a potent antioxidant with established effects attributed largely to a key ingredient anthraquinone. This study investigated the inhibitory ability of the three anthraquinones from A. vera on the formation of AGEs in a heated model system at 70°C. Anthraquinones, including aloe‐emodin (AED), emodin (ED), and chrysophanol (CSN), were extracted from A. vera and analyzed by ultra‐high performance liquid chromatography‐tandem mass spectrometry. Under optimal extraction conditions, the extraction yield of the anthraquinones was 4.377 mg/g. Anthraquinones showed good inhibition toward the formation of glycation products; the inhibition rates of AED, ED, and CSN on crosslinked AGEs were 46.48%, 66.38%, and 57.32% at 10 μM concentrations. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis images also proved that the anthraquinones could significantly inhibit crosslinked AGE formation in a time‐dependent manner. ED showed higher inhibitory ability than AED and CSN on the formation of Nɛ‐(carboxymethyl)lysine and crosslinked AGEs. The results indicate that the antiglycation properties of these anthraquinones are likely related to the phenolic hydroxyl groups in their structures, but this ability is not related to their antioxidant activity, which probably depends on the whole structure of the quinone. Generally, the anthraquinones in A. vera, especially ED, can effectively inhibit AGE formation and reduce protein crosslinking during food processing, even at low concentration. Practical applications The inhibitory effects of three anthraquinones extracted from Aloe vera on the formation of AGEs were investigated in a heated model system. The results indicate Aloe can be used as an effective inhibitor of glycation products in food processing, moreover, this research can be useful for finding suitable nature inhibitors of AGEs for food processing.

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“…Anthraquinone derivatives show a wide array of pharmacological activities including laxative, 25,26 anticancer, [27][28][29][30] antiinflammatory, 31 antiarthritic, 32 antifungal, 33 antibacterial, 34 antiviral, 35 antiplatelet, [36][37][38] and neuroprotective effects. 39 In addition, they have shown potential for the treatment of malaria 40 and multiple sclerosis 41 ; and there is continued interest in the development of new anthraquinone derivatives displaying biological activities.…”

Section: Anthraquinones As Drugsmentioning

confidence: 99%

Anthraquinones As Pharmacological Tools and Drugs

Malik

Müller

2016

Medicinal Research Reviews

337

211

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Anthraquinones (9,10-dioxoanthracenes) constitute an important class of natural and synthetic compounds with a wide range of applications. Besides their utilization as colorants, anthraquinone derivatives have been used since centuries for medical applications, for example, as laxatives and antimicrobial and antiinflammatory agents. Current therapeutic indications include constipation, arthritis, multiple sclerosis, and cancer. Moreover, biologically active anthraquinones derived from Reactive Blue 2 have been utilized as valuable tool compounds for biochemical and pharmacological studies. They may serve as lead structures for the development of future drugs. However, the presence of the quinone moiety in the structure of anthraquinones raises safety concerns, and anthraquinone laxatives have therefore been under critical reassessment. This review article provides an overview of the chemistry, biology, and toxicology of anthraquinones focusing on their application as drugs.

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A mode of action study of cationic anthraquinone analogs: a new class of highly potent anticancer agents

Cited by 51 publications

References 29 publications

Discorhabdin N, a South African Natural Compound, for Hsp72 and Hsc70 Allosteric Modulation: Combined Study of Molecular Modeling and Dynamic Residue Network Analysis

Discorhabdin N, a South African Natural Compound, for Hsp72 and Hsc70 Allosteric Modulation: Combined Study of Molecular Modeling and Dynamic Residue Network Analysis

Main anthraquinone components in Aloe vera and their inhibitory effects on the formation of advanced glycation end-products

Anthraquinones As Pharmacological Tools and Drugs

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