Publication: Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents
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Issued Date
2014
Resource Type
File Type
application/pdf
ISSN
2235234
Other identifier(s)
2-s2.0-84905161366
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
European Journal of Medicinal Chemistry. Vol 85, (2014), p.65-76
Suggested Citation
Pingaew R., Saekee A., Mandi P., Nantasenamat C., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents. European Journal of Medicinal Chemistry. Vol 85, (2014), p.65-76. doi:10.1016/j.ejmech.2014.07.087 Retrieved from: https://hdl.handle.net/20.500.14740/6312
Abstract
A new series of chalcone-coumarin derivatives (9-19) linked by the 1,2,3-triazole ring were synthesized through the azide/alkyne dipolar cycloaddition. Hybrid molecules were evaluated for their cytotoxic activity against four cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) and antimalarial activity toward Plasmodium falciparum. Most of the synthesized hybrids, except for analogs 10 and 16, displayed cytotoxicity against MOLT-3 cell line without affecting normal cells. Analogs (10, 11, 16 and 18) exhibited higher inhibitory efficacy than the control drug, etoposide, in HepG2 cells. Significantly, the high cytotoxic potency of the hybrid 11 was shown to be non-toxic to normal cells. Interestingly, the chalcone-coumarin 18 was the most potent antimalarial compound affording IC50 value of 1.60 μM. Molecular docking suggested that the cytotoxicity of reported hybrids could be possibly due to their dual inhibition of α- and β-tubulins at GTP and colchicine binding sites, respectively. Furthermore, falcipain-2 was identified to be a plausible target site of the hybrids given their antimalarial potency. © 2014 Elsevier Masson SAS. All rights reserved.
Subject(s)
4 ((1 (3 (3 (2,3 dimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
4 ((1 (3 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
4 ((1 (3 (3 (3,4 dimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
4 ((1 (4 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
4 ((1 (4 (3 (3,4,5 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yll)methoxy) 2h chromen 2 one
7 ((1 (3 (3 (2,3 dimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (3 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (3 (3 (3,4 dimethoxyphenyl)acryloyl)phenyl) 1 h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (4 (3 (2,3 dimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (4 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (4 (3 (3,4,5 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
Alpha tubulin
Antimalarial agent
Antineoplastic agent
Beta tubulin
Chalcone derivative
Coumarin derivative
Etoposide
Falcipain 2
Unclassified drug
1,2,3 triazole derivative
4 [[1 [3 [3 (2,3 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [3 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [3 [3 (3,4 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [4 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [4 [3 (3,4,5 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [3 (2,3 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [3 (3,4 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [4 [3 (2,3 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [4 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [4 [3 (3,4,5 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
Antimalarial agent
Antineoplastic agent
Chalcone derivative
Colchicine
Coumarin derivative
Dihydroartemisinin
Doxorubicin
Ellipticine
Etoposide
Falcipain 2
N [n (3 carboxyoxirane 2 carbonyl)leucyl]agmatine
Tubulin
Antimalarial agent
Antineoplastic agent
Chalcone
Coumarin
Coumarin derivative
Cysteine proteinase
Triazole derivative
Antimalarial activity
Antineoplastic activity
Article
Cancer cell line
Carbon nuclear magnetic resonance
Cycloaddition
Cytotoxicity
Drug structure
Drug synthesis
HepG2 cell line
Human
Human cell
Molecular docking
Plasmodium falciparum
Proton nuclear magnetic resonance
A549 cell line
AGMK cell line
Animal cell
Antimalarial activity
Article
Cholangiocarcinoma cell line
Controlled study
Crystal structure
Drug binding site
Drug cytotoxicity
Drug potency
Drug screening
Drug synthesis
Hydrogen bond
IC50
Leukemia cell line
Lymphatic leukemia
Molecular docking
Nonhuman
Structure activity relation
Vero cell line
Chemistry
Drug effects
Metabolism
Protein conformation
Synthesis
Tumor cell line
Antimalarials
Antineoplastic Agents
Cell Line, Tumor
Chalcone
Chemistry Techniques, Synthetic
Coumarins
Cysteine Endopeptidases
Humans
Molecular Docking Simulation
Plasmodium falciparum
Protein Conformation
Triazoles
Tubulin
4 ((1 (3 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
4 ((1 (3 (3 (3,4 dimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
4 ((1 (4 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
4 ((1 (4 (3 (3,4,5 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yll)methoxy) 2h chromen 2 one
7 ((1 (3 (3 (2,3 dimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (3 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (3 (3 (3,4 dimethoxyphenyl)acryloyl)phenyl) 1 h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (4 (3 (2,3 dimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (4 (3 (2,3,4 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
7 ((1 (4 (3 (3,4,5 trimethoxyphenyl)acryloyl)phenyl) 1h 1,2,3 triazol 4 yl)methoxy) 2h chromen 2 one
Alpha tubulin
Antimalarial agent
Antineoplastic agent
Beta tubulin
Chalcone derivative
Coumarin derivative
Etoposide
Falcipain 2
Unclassified drug
1,2,3 triazole derivative
4 [[1 [3 [3 (2,3 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [3 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [3 [3 (3,4 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [4 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
4 [[1 [4 [3 (3,4,5 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [3 (2,3 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [3 [3 (3,4 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [4 [3 (2,3 dimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [4 [3 (2,3,4 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
7 [[1 [4 [3 (3,4,5 trimethoxyphenyl)acryloyl]phenyl] 1h 1,2,3 triazol 4 yl]methoxy] 2h chromen 2 one
Antimalarial agent
Antineoplastic agent
Chalcone derivative
Colchicine
Coumarin derivative
Dihydroartemisinin
Doxorubicin
Ellipticine
Etoposide
Falcipain 2
N [n (3 carboxyoxirane 2 carbonyl)leucyl]agmatine
Tubulin
Antimalarial agent
Antineoplastic agent
Chalcone
Coumarin
Coumarin derivative
Cysteine proteinase
Triazole derivative
Antimalarial activity
Antineoplastic activity
Article
Cancer cell line
Carbon nuclear magnetic resonance
Cycloaddition
Cytotoxicity
Drug structure
Drug synthesis
HepG2 cell line
Human
Human cell
Molecular docking
Plasmodium falciparum
Proton nuclear magnetic resonance
A549 cell line
AGMK cell line
Animal cell
Antimalarial activity
Article
Cholangiocarcinoma cell line
Controlled study
Crystal structure
Drug binding site
Drug cytotoxicity
Drug potency
Drug screening
Drug synthesis
Hydrogen bond
IC50
Leukemia cell line
Lymphatic leukemia
Molecular docking
Nonhuman
Structure activity relation
Vero cell line
Chemistry
Drug effects
Metabolism
Protein conformation
Synthesis
Tumor cell line
Antimalarials
Antineoplastic Agents
Cell Line, Tumor
Chalcone
Chemistry Techniques, Synthetic
Coumarins
Cysteine Endopeptidases
Humans
Molecular Docking Simulation
Plasmodium falciparum
Protein Conformation
Triazoles
Tubulin