Design and Development of Halogenated Chalcone Derivatives as Potential Anticancer Agents

Jain, Upendra Kumar; Bhatia, Richa Kaur; Akkinepally, Raghuram Rao; Singh, Ranjit; Saxena, Ajit Kumar; Sehar, Irum

doi:10.4314/tjpr.v13i1.11

Cited by 51 publications

(12 citation statements)

References 20 publications

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“…The docking results of three crystal structures were intersected. The docking score, key residues and binding poses were analyzed for selecting the potential oligopeptides [46,47]. The obtained oligopeptides were further evaluated by biochemistry assay and MD.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…3) chalcones, suggesting molecular variations were relevant for antiproliferative screening against both cell lines. Experiments at 20 lM allowed us to derive preliminary structural features related to antiproliferative activity [28][29][30] .…”

Section: Antiproliferative Activity Of Chalcones 1-20mentioning

confidence: 99%

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

Santos

Anselmo

Oliveira

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Chalcones are valuable structures for drug discovery due to their broad bioactivity spectrum. In this study, we evaluated 20 synthetic chalcones against estrogen-receptor-positive breast cancer cells (MCF-7 line) and triple-negative breast cancer (TNBC) cells (MDA-MB-231 line). Antiproliferative screening by MTT assay resulted in two most active compounds: 2-fluoro-4'-aminochalcone (11) and 3-pyridyl-4'-aminochalcone (17). Their IC 50 values ranged from 13.2 to 34.7 mM against both cell lines. Selected chalcones are weak basic compounds and maintained their antiproliferative activity under acidosis conditions (pH 6.7), indicating their resistance to ion-trapping effect. The mode of breast cancer cells death was investigated and chalcones 11 and 17 were able to induce apoptosis rather than necrosis in both lines. Antiproliferative target investigations with MCF-7 cells suggested 11 and 17 upregulated p53 protein expression and did not affect Sp1 protein expression. Future studies on chalcones 11 and 17 can define their in vivo therapeutic potential.

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“…The drugs and drug candidate compounds developed by medicinal chemistry studies include a significant number of halogenated structures. [ 47,48 ] Some halogen‐substituted chalcones were reported with strong cytotoxic activities [ 28,49–51 ] in a limited number of studies.…”

Section: Introductionmentioning

confidence: 99%

New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6‐(3‐Halogenated phenyl‐2‐propen‐1‐oyl)‐2(3H)‐benzoxazolones

Bilginer

Gül

Erdal

et al. 2020

Archiv der Pharmazie

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In this study, novel halogenated chalcones, 6-(3-halogenated phenyl-2-propen-1-one)-2(3H)-benzoxazolones (2a-n), were synthesized for the first time (except 2a), and their chemical structures were characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectrometry spectra. Cytotoxic activities and carbonic anhydrase (CA) inhibitory effects of the compounds were studied to identify new possible drug candidate molecules. Cytotoxicity results pointed out that compound 2m, 6-[3-(3-bromophenyl)-2-propenoyl]-2(3H)-benzoxazolone, had the highest cytotoxicity (CC 50 ) and potency selectivity expression (PSE) values. Thus, compound 2m can be considered as a lead compound of the series in terms of cytotoxicity. When the CA inhibition results of the compounds were evaluated, it was found that the K i values of the compounds ranged from 30.5 ± 11.3 to 65.5 ± 25.6 µM toward hCA I, and they ranged from 7.3 ± 1.8 to 58.8 ± 12.3 µM toward hCA II. However, the K i values of the reference drug, acetazolamide (AZA), were 30.2 ± 7.8 and 4.4 ± 0.6 μM toward hCA I and hCA II, respectively. According to the results obtained, compounds 2a-n had lower K i values than AZA, whereas compounds 2a, 2b, 2e-g, 2l, and 2n had similar K i values, compared with AZA. So, the compounds 2a, 2b, 2e-g, 2l, and 2n can be considered as lead molecules of this series for further considerations.

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Design and Development of Halogenated Chalcone Derivatives as Potential Anticancer Agents

Cited by 51 publications

References 20 publications

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

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

Antiproliferative activity and p53 upregulation effects of chalcones on human breast cancer cells

New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6‐(3‐Halogenated phenyl‐2‐propen‐1‐oyl)‐2(3H)‐benzoxazolones

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