Design, Synthesis, and Biological Evaluation of 2-(2-Bromo-3-nitrophenyl)-5-phenyl-1,3,4-oxadiazole Derivatives as Possible Anti-Breast Cancer Agents.
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Binding Sites
Breast Neoplasms
/ metabolism
Cell Line, Tumor
DNA (Cytosine-5-)-Methyltransferase 1
/ antagonists & inhibitors
Drug Design
Drug Screening Assays, Antitumor
Enzyme Inhibitors
/ chemistry
Estrogen Receptor alpha
/ chemistry
Female
Humans
Imatinib Mesylate
/ pharmacology
Molecular Conformation
Molecular Docking Simulation
Oxadiazoles
/ chemistry
Structure-Activity Relationship
1,3,4-oxadiazole
ADMET
breast cancer
cytotoxicity
estrogen receptor
molecular dynamics
single-crystal XRD
Journal
Chemistry & biodiversity
ISSN: 1612-1880
Titre abrégé: Chem Biodivers
Pays: Switzerland
ID NLM: 101197449
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
20
11
2019
accepted:
07
01
2020
pubmed:
30
1
2020
medline:
11
3
2020
entrez:
30
1
2020
Statut:
ppublish
Résumé
Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940's. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2-(2-bromo-3-nitrophenyl)-5-phenyl-1,3,4-oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4-oxadiazole derivatives 4a-4j have been synthesized and described by spectroscopic method. 2-(2-Bromo-6-nitrophenyl)-5-(4-bromophenyl)-1,3,4-oxadiazole (4c) was reconfirmed by single-crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF-7, MDA-MB-453 and MCF-10A non-cancer cell lines. The compounds with the methoxy (in 4c) and methyl (in 4j) substitution were shown to have significant cytotoxicity, with 4c showing dose-dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein-ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.
Identifiants
pubmed: 31995280
doi: 10.1002/cbdv.201900659
doi:
Substances chimiques
Antineoplastic Agents
0
Enzyme Inhibitors
0
Estrogen Receptor alpha
0
Oxadiazoles
0
1,3,4-oxadiazole
20O2F20OUR
Imatinib Mesylate
8A1O1M485B
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
DNMT1 protein, human
EC 2.1.1.37
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1900659Informations de copyright
© 2020 Wiley-VHCA AG, Zurich, Switzerland.
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