Publication: Synthesis, molecular docking, and QSAR study of bis-sulfonamide derivatives as potential aromatase inhibitors
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0
Issued Date
2019
Resource Type
File Type
application/pdf
ISSN
9680896
Other identifier(s)
2-s2.0-85070395327
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
Bioorganic and Medicinal Chemistry. Vol 27, No.19 (2019)
Suggested Citation
Leechaisit R., Pingaew R., Prachayasittikul V., Worachartcheewan A., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Synthesis, molecular docking, and QSAR study of bis-sulfonamide derivatives as potential aromatase inhibitors. Bioorganic and Medicinal Chemistry. Vol 27, No.19 (2019). doi:10.1016/j.bmc.2019.08.001 Retrieved from: https://hdl.handle.net/20.500.14740/5135
Abstract
A library of bis-sulfonamides (9–26) were synthesized and tested for their aromatase inhibitory activities. Interestingly, all bis-sulfonamide derivatives inhibited the aromatase with IC50 range of 0.05–11.6 μM except for compound 23. The analogs 15 and 16 bearing hydrophobic chloro and bromo groups exhibited the potent aromatase inhibitory activity in sub-micromolar IC50 values (i.e., 50 and 60 nM, respectively) with high safety index. Molecular docking revealed that the chloro and bromo benzenesulfonamides (15 and 16) may play role in the hydrophobic interaction with Leu477 of the aromatase to mimic steroidal backbone of the natural substrate, androstenedione. QSAR study also revealed that the most potent activity of compounds was governed by van der Waals volume (GATS6v) and mass (Mor03m) descriptors. Finally, the two compounds (15 and 16) were highlighted as promising compounds to be further developed as novel aromatase inhibitors. © 2019 Elsevier Ltd
Subject(s)
Androstenedione
Aromatase
Benzenesulfonamide derivative
Doxorubicin
Letrozole
N,n' (1,3 phenylene)bis(4 chlorobenzenesulfonamide)
N,n' (1,3 phenylene)bis(4 methoxybenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(2 nitrobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(2,3,5,6 tetramethylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(3 aminobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(3 nitrobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 acetylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 bromobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 chlorobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 cyanobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 fluorobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 methoxybenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 methylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 nitrobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 trifluoromethylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(naphthalene 2 sulfonamide)
N,n' [1,4 phenylenebis(methylene)]bis(2,3,5,6 tetramethylbenzenesulfonamide)
N,n' [1,4 phenylenebis(methylene)]bis(4 cyanobenzenesulfonamide)
Sulfonamide
Unclassified drug
Aromatase
Aromatase inhibitor
Protein binding
Sulfonamide
Article
Breast cancer
Controlled study
Drug cytotoxicity
Drug potency
Drug safety
Drug structure
Drug synthesis
Enzyme inhibition
Hydrophobicity
IC50
Molecular docking
MRC-5 cell line
Quantitative structure activity relation
Structure activity relation
T-47D cell line
Binding site
Chemical structure
Chemistry
Human
Metabolism
Molecular library
Pharmacology
Synthesis
Tumor cell line
Aromatase
Aromatase Inhibitors
Binding Sites
Cell Line, Tumor
Humans
Molecular Docking Simulation
Molecular Structure
Protein Binding
Quantitative Structure-Activity Relationship
Small Molecule Libraries
Sulfonamides
Aromatase
Benzenesulfonamide derivative
Doxorubicin
Letrozole
N,n' (1,3 phenylene)bis(4 chlorobenzenesulfonamide)
N,n' (1,3 phenylene)bis(4 methoxybenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(2 nitrobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(2,3,5,6 tetramethylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(3 aminobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(3 nitrobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 acetylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 bromobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 chlorobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 cyanobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 fluorobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 methoxybenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 methylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 nitrobenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(4 trifluoromethylbenzenesulfonamide)
N,n' [1,3 phenylenebis(methylene)]bis(naphthalene 2 sulfonamide)
N,n' [1,4 phenylenebis(methylene)]bis(2,3,5,6 tetramethylbenzenesulfonamide)
N,n' [1,4 phenylenebis(methylene)]bis(4 cyanobenzenesulfonamide)
Sulfonamide
Unclassified drug
Aromatase
Aromatase inhibitor
Protein binding
Sulfonamide
Article
Breast cancer
Controlled study
Drug cytotoxicity
Drug potency
Drug safety
Drug structure
Drug synthesis
Enzyme inhibition
Hydrophobicity
IC50
Molecular docking
MRC-5 cell line
Quantitative structure activity relation
Structure activity relation
T-47D cell line
Binding site
Chemical structure
Chemistry
Human
Metabolism
Molecular library
Pharmacology
Synthesis
Tumor cell line
Aromatase
Aromatase Inhibitors
Binding Sites
Cell Line, Tumor
Humans
Molecular Docking Simulation
Molecular Structure
Protein Binding
Quantitative Structure-Activity Relationship
Small Molecule Libraries
Sulfonamides