Publication: Synthesis and molecular docking of 1,2,3-triazole-based sulfonamides as aromatase inhibitors
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0
Issued Date
2015
Resource Type
File Type
application/pdf
ISSN
9680896
Other identifier(s)
2-s2.0-84937425435
Rights Holder(s)
Scopus
Bibliographic Citation
Bioorganic and Medicinal Chemistry. Vol 23, No.13 (2015), p.3472-3480
Suggested Citation
Pingaew R., Prachayasittikul V., Mandi P., Nantasenamat C., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Synthesis and molecular docking of 1,2,3-triazole-based sulfonamides as aromatase inhibitors. Bioorganic and Medicinal Chemistry. Vol 23, No.13 (2015), p.3472-3480. doi:10.1016/j.bmc.2015.04.036 Retrieved from: https://hdl.handle.net/20.500.14740/6253
Abstract
Abstract A series of 1,4-disubstituted-1,2,3-triazoles (13-35) containing sulfonamide moiety were synthesized and evaluated for their aromatase inhibitory effects. Most triazoles with open-chain sulfonamide showed significant aromatase inhibitory activity (IC50 = 1.3-9.4 μM). Interestingly, the meta analog of triazole-benzene-sulfonamide (34) bearing 6,7-dimethoxy substituents on the isoquinoline ring displayed the most potent aromatase inhibitory activity (IC50 = 0.2 μM) without affecting normal cell. Molecular docking of these triazoles against aromatase revealed that the compounds could snugly occupy the active site of the enzyme through hydrophobic, π-π stacking, and hydrogen bonding interactions. The potent compound 34 was able to form hydrogen bonds with Met374 and Ser478 which were suggested to be the essential residues for the promising inhibition. The study provides compound 34 as a potential lead molecule of anti-aromatase agent for further development. © 2015 Elsevier Ltd.
Subject(s)
1,2,3 triazole derivative
1,2,3 triazole sulfonamide derivative
4 [[1 [3 [(3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [3 [(6,7 dimethoxy 3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [(3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [(6,7 dimethoxy 3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
Aromatase inhibitor
Coumarin oxymethyl
Functional group
Ketoconazole
Letrozole
Naphthalene oxymethyl
Phenoxymethyl
Phenyl group
Sulfonamide
Sulfonyl group
Unclassified drug
Antineoplastic agent
Aromatase
Aromatase inhibitor
CYP19A1 protein, human
Isoquinoline derivative
Protein binding
Sulfonamide
Triazole derivative
Animal cell
Article
Binding affinity
Binding site
Carbon nuclear magnetic resonance
Chemical interaction
Chemical reaction
Click reaction
Concentration response
Controlled study
Drug cytotoxicity
Drug mechanism
Drug potency
Drug safety
Drug screening
Drug synthesis
Enzyme active site
Enzyme inhibition
Hydrogen bond
Hydrophobicity
IC50
Mass spectrometry
Molecular docking
Nonhuman
Pi pi stacking interaction
Proton nuclear magnetic resonance
Structure activity relation
Vero cell line
Animal
Cell survival
Chemical phenomena
Chemistry
Chlorocebus aethiops
Drug effects
Human
Synthesis
Animals
Antineoplastic Agents
Aromatase
Aromatase Inhibitors
Catalytic Domain
Cell Survival
Cercopithecus aethiops
Humans
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Isoquinolines
Molecular Docking Simulation
Protein Binding
Structure-Activity Relationship
Sulfonamides
Triazoles
Vero Cells
1,2,3 triazole sulfonamide derivative
4 [[1 [3 [(3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [3 [(6,7 dimethoxy 3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [(3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [(6,7 dimethoxy 3,4 dihydroisoquinolin 2 (1h)yl)sulfonyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
Aromatase inhibitor
Coumarin oxymethyl
Functional group
Ketoconazole
Letrozole
Naphthalene oxymethyl
Phenoxymethyl
Phenyl group
Sulfonamide
Sulfonyl group
Unclassified drug
Antineoplastic agent
Aromatase
Aromatase inhibitor
CYP19A1 protein, human
Isoquinoline derivative
Protein binding
Sulfonamide
Triazole derivative
Animal cell
Article
Binding affinity
Binding site
Carbon nuclear magnetic resonance
Chemical interaction
Chemical reaction
Click reaction
Concentration response
Controlled study
Drug cytotoxicity
Drug mechanism
Drug potency
Drug safety
Drug screening
Drug synthesis
Enzyme active site
Enzyme inhibition
Hydrogen bond
Hydrophobicity
IC50
Mass spectrometry
Molecular docking
Nonhuman
Pi pi stacking interaction
Proton nuclear magnetic resonance
Structure activity relation
Vero cell line
Animal
Cell survival
Chemical phenomena
Chemistry
Chlorocebus aethiops
Drug effects
Human
Synthesis
Animals
Antineoplastic Agents
Aromatase
Aromatase Inhibitors
Catalytic Domain
Cell Survival
Cercopithecus aethiops
Humans
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Isoquinolines
Molecular Docking Simulation
Protein Binding
Structure-Activity Relationship
Sulfonamides
Triazoles
Vero Cells