Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as FAK inhibitors with anticancer activity

Duan, Yongtao; Yao, Y. Lawrence; Huang, Wei; Makawana, Jigar A.; Teraiya, Shashikant B.; Thumar, Nilesh J.; Tang, Dan-Jie; Tao, Xiang-Xiang; Wang, Zhongchang; Jiang, Aiqin; Zhu, Hai‐Liang

doi:10.1016/j.bmc.2014.04.005

Cited by 22 publications

(16 citation statements)

References 25 publications

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“…The −CDOCKER energy and −CDOCKER interaction energy values are showed in Table . −CDOCKER energy is the scoring function of the CDOCKER algorithm, which represents the energy of the ligand–receptor complexes . When trying to identify the most effective binder to a given target between a set of different ligands, the binding energy is thought to be the best choice .…”

Section: Resultsmentioning

confidence: 99%

Identification and molecular docking study of novel angiotensin‐converting enzyme inhibitory peptides from Salmo salar using in silico methods

Chen

Zhao

et al. 2018

J Sci Food Agric

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Section: Resultsmentioning

confidence: 99%

Identification and molecular docking study of novel angiotensin‐converting enzyme inhibitory peptides from Salmo salar using in silico methods

Chen

Zhao

et al. 2018

J Sci Food Agric

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“…The docking models with different sphere radius might be beneficial for the distinguishing potential active oligopeptides. –CDOCKER ENERGY (kcal/mol) was the scoring function of CDOCKER algorithm, which represented the energy of the ligand–receptor complexes [35]. Fifty percent of –CDOCKER ENERGY for three crystal structures were regarded as the threshold for screening the potential ACE inhibitory oligopeptides [36,37].…”

Section: Resultsmentioning

confidence: 99%

Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

Qiao

Chen

et al. 2016

IJMS

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Adlay (Coix larchryma-jobi L.) was the commonly used Traditional Chinese Medicine (TCM) with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE) was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM), was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC) assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM) proteins based on in silico proteolysis and virtual screening, which could be beneficial to reveal the pharmacological action of TCM proteins and provide new lead compounds for peptides-based drug design.

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“…The binding site was carried out with a radius of 17.258 Å, with coordinates x : 40.498, y : 34.883, and z : 44.382. The pose of each ligand was selected based on the interaction energy (Duan et al, ). DS was used to distinguish salt bridge, conventional hydrogen bond, carbon hydrogen bond, pi‐alkyl, van de Waals, alkyl, and metal‐acceptor bond at the ACE active sites (Guo et al, ).…”

Section: Methodsmentioning

confidence: 99%

Novel ACE inhibitors derived from soybean proteins using in silico and in vitro studies

Zhao

Xue

et al. 2019

J Food Biochem

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The widespread application of soybean‐derived peptides is currently limited due to the challenges in the identification of peptides. In the present work, in silico and in vitro analysis were applied to identify ACE inhibitory tri‐peptides from soybean protein. The soybean protein was cleaved by PeptideCutter. Then, unknown tri‐peptides were selected to solubility estimation and ADME prediction. Subsequently, Discovery Studio was applied to evaluate the interaction mechanism between ACE and tri‐peptides. Finally, in vitro activity of theoretical ACE inhibitory tri‐peptides was verified by RP‐HPLC method. As a result, DMG was selected as a potent ACE inhibitory peptide. Cell experiment showed that DMG had no cytotoxic effects on HEK‐293 cells. And molecular docking results indicated that DMG contacted well with ACE’s active sites (Gln281, His353, Ala354, Glu384, Lys511, His513, and Tyr520). Furthermore, DMG could exert potent activity against ACE, with IC50 value of 3.95 ± 0.11 mM. Practical applications Present research showed soybean is a potential protein resource to obtain ACE inhibitory peptides. Simultaneously, virtual screening method is a feasible way to substitute for classical method in emerging nutritional fields. What's more, present study provides a theoretical basis for industrial research on foodstuff for ACE inhibitory peptides without side effects.

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Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as FAK inhibitors with anticancer activity

Cited by 22 publications

References 25 publications

Identification and molecular docking study of novel angiotensin‐converting enzyme inhibitory peptides from Salmo salar using in silico methods

Identification and molecular docking study of novel angiotensin‐converting enzyme inhibitory peptides from Salmo salar using in silico methods

Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

Novel ACE inhibitors derived from soybean proteins using in silico and in vitro studies

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