Publication: Synthesis and molecular docking of N,N′-disubstituted thiourea derivatives as novel aromatase inhibitors
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0
Issued Date
2018
Resource Type
File Type
application/pdf
ISSN
452068
Other identifier(s)
2-s2.0-85046814081
Rights Holder(s)
Scopus
Bibliographic Citation
Bioorganic Chemistry. Vol 79, (2018), p.171-178
Suggested Citation
Pingaew R., Prachayasittikul V., Anuwongcharoen N., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Synthesis and molecular docking of N,N′-disubstituted thiourea derivatives as novel aromatase inhibitors. Bioorganic Chemistry. Vol 79, (2018), p.171-178. doi:10.1016/j.bioorg.2018.05.002 Retrieved from: https://hdl.handle.net/20.500.14740/5887
Abstract
A three series of thioureas, monothiourea type I (4a–g), 1,4-bisthiourea type II (5a–h) and 1,3-bisthiourea type III (6a–h) were synthesized. Their aromatase inhibitory activities have been evaluated. Interestingly, eight thiourea derivatives (4e, 5f–h, 6d, 6f–h) exhibited the aromatase inhibitory activities with IC50 range of 0.6–10.2 μM. The meta-bisthiourea bearing 4-NO2 group (6f) and 3,5-diCF3 groups (6h) were shown to be the most potent compounds with sub-micromolar IC50 values of 0.8 and 0.6 μM, respectively. Molecular docking also revealed that one of the thiourea moieties of these two compounds could mimic steroidal backbone of the natural androstenedione (ASD) via hydrophobic interactions with enzyme residues (Val370, Leu477, Thr310, and Phe221 for 6f, Val370, Leu477, Ser478, and Ile133 for 6h). This is the first time that the bisthioureas have been reported for their potential to be developed as aromatase inhibitors, in which the 4-NO2 and 3,5-diCF3 analogs have been highlighted as promising candidates. © 2018 Elsevier Inc.
Subject(s)
1 benzyl 3 (3,5 ditrifluoromethylphenyl)thiourea
1 benzyl 3 (4 bromophenyl)thiourea
1 benzyl 3 (4 chlorophenyl)thiourea
1 benzyl 3 (4 fluorophenyl)thiourea
1 benzyl 3 (4 methoxyphenyl)thiourea
1 benzyl 3 (4 nitrophenyl)thiourea
1 benzyl 3 (4 trifluoromethylphenyl)thiourea
1,1' [1,3 phenylenebis(methylene)]bis[3 (4 fluorophenyl)thiourea]
1,1' [1,4 phenylenebis(methylene)]bis[3 (4 fluorophenyl)thiourea]
Androstenedione
Aromatase inhibitor
Doxorubicin
Isoleucine
Letrozole
Leucine
Phenylalanine
Serine
Thiourea derivative
Threonine
Unclassified drug
Valine
Antineoplastic agent
Aromatase
Aromatase inhibitor
Thiourea
Antineoplastic activity
Article
Breast cancer
Controlled study
Cytotoxicity
Cytotoxicity assay
Drug potency
Drug synthesis
Enzyme inhibition
Human
Hydrophobicity
IC50
MCF-7 cell line
Molecular docking
Phenotype
Priority journal
Analogs and derivatives
Binding site
Chemical phenomena
Chemical structure
Chemistry
Molecular docking
Synthesis
Antineoplastic Agents
Aromatase
Aromatase Inhibitors
Binding Sites
Humans
Hydrophobic and Hydrophilic Interactions
MCF-7 Cells
Molecular Docking Simulation
Molecular Structure
Thiourea
1 benzyl 3 (4 bromophenyl)thiourea
1 benzyl 3 (4 chlorophenyl)thiourea
1 benzyl 3 (4 fluorophenyl)thiourea
1 benzyl 3 (4 methoxyphenyl)thiourea
1 benzyl 3 (4 nitrophenyl)thiourea
1 benzyl 3 (4 trifluoromethylphenyl)thiourea
1,1' [1,3 phenylenebis(methylene)]bis[3 (4 fluorophenyl)thiourea]
1,1' [1,4 phenylenebis(methylene)]bis[3 (4 fluorophenyl)thiourea]
Androstenedione
Aromatase inhibitor
Doxorubicin
Isoleucine
Letrozole
Leucine
Phenylalanine
Serine
Thiourea derivative
Threonine
Unclassified drug
Valine
Antineoplastic agent
Aromatase
Aromatase inhibitor
Thiourea
Antineoplastic activity
Article
Breast cancer
Controlled study
Cytotoxicity
Cytotoxicity assay
Drug potency
Drug synthesis
Enzyme inhibition
Human
Hydrophobicity
IC50
MCF-7 cell line
Molecular docking
Phenotype
Priority journal
Analogs and derivatives
Binding site
Chemical phenomena
Chemical structure
Chemistry
Molecular docking
Synthesis
Antineoplastic Agents
Aromatase
Aromatase Inhibitors
Binding Sites
Humans
Hydrophobic and Hydrophilic Interactions
MCF-7 Cells
Molecular Docking Simulation
Molecular Structure
Thiourea