Discovery and molecular docking of quinolyl-thienyl chalcones as anti-angiogenic agents targeting VEGFR-2 tyrosine kinase

Rizvi, Syed Umar Farooq; Siddiqui, Hamid Latif; Nisar, Muhammad; Khan, Naeem; Khan, Inamullah

doi:10.1016/j.bmcl.2011.12.017

Cited by 45 publications

(29 citation statements)

References 15 publications

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“…This was correlated with decreased endothelial growth as well as VEGF-stimulated tumor growth in two xenograft models, due in part to decreased vessel density. In a structure-based virtual screening, Rizvi et al [118] identified a series of quinolyl-thienyl chalcones as potent VEGFR-2 kinase inhibitors with IC 50 of 73.41 nM for the lead compound. Interestingly, several authors have reported that the effect of chalcones on endothelial cells, including decreased proliferation and apoptosis, seem to occur at very low concentrations when compared to those needed to reach IC 50 levels in tumor cells.…”

Section: Chalcones Target the Tumor Vasculaturementioning

confidence: 99%

Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

Jandial¹,

Blair²,

Zhang³

et al. 2014

CCDT

114

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There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy.

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Section: Chalcones Target the Tumor Vasculaturementioning

confidence: 99%

Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

Jandial¹,

Blair²,

Zhang³

et al. 2014

CCDT

114

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“…OEDocking 3.0.0 (Santa Fe, NM) [18][19][20][21][22] was used in this study to dock the OMEGA pre-generated multi-conformer library. FRED strategy was used, which exhaustively dock/score all possible positions of each ligand in the binding site.…”

Section: Molecular Docking Simulationsmentioning

confidence: 99%

Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana

Shah

Ishtiaq

Hizbullah

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Artemisia roxburghiana is used in traditional medicine for treating various diseases including diabetes. The present study was designed to evaluate the antidiabetic potential of active constituents by using protein tyrosine phosphatase 1B (PTP1B) as a validated target for management of diabetes. Various compounds were isolated as active principles from the crude methanolic extract of aerial parts of A. roxburghiana. All compounds were screened for PTP1B inhibitory activity. Molecular docking simulations were performed to investigate the mechanism behind PTP1B inhibition of the isolated compound and positive control, ursolic acid. Betulinic acid, betulin and taraxeryl acetate were the active PTP1B principles with IC 50 values 3.49 ± 0.02, 4.17 ± 0.03 and 87.52 ± 0.03 mM, respectively. Molecular docking studies showed significant molecular interactions of the triterpene inhibitors with Gly220, Cys215, Gly218 and Asp48 inside the active site of PTP1B. The antidiabetic activity of A. roxburghiana could be attributed due to PTP1B inhibition by its triterpene constituents, betulin, betulinic acid and taraxeryl acetate. Computational insights of this study revealed that the C-3 and C-17 positions of the compounds needs extensive optimization for the development of new lead compounds.

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“…They have been shown to possess antibacterial, anti-protozoal, anti-malarial (Hayat et al, 2011) and anti-inflammatory activities (Gómez-Rivera et al, 2013). The compound selected for current investigations was synthesized as reported earlier (Rizvi et al, 2012). Previously vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitory activity of the same compound was investigated (Rizvi et al, 2012).…”

mentioning

confidence: 99%

“…The compound selected for current investigations was synthesized as reported earlier (Rizvi et al, 2012). Previously vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitory activity of the same compound was investigated (Rizvi et al, 2012). …”

mentioning

confidence: 99%