Publication: Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives
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Issued Date
2014
Resource Type
File Type
application/pdf
ISSN
2235234
Other identifier(s)
2-s2.0-84904286268
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
European Journal of Medicinal Chemistry. Vol 84, (2014), p.247-263
Suggested Citation
Prachayasittikul V., Pingaew R., Worachartcheewan A., Nantasenamat C., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives. European Journal of Medicinal Chemistry. Vol 84, (2014), p.247-263. doi:10.1016/j.ejmech.2014.07.024 Retrieved from: https://hdl.handle.net/20.500.14740/6377
Abstract
A series of 2-substituted amino-3-chloro-1,4-naphthoquinone derivatives (3-12) were synthesized as anticancer agents and tested against four cancer cell lines including HepG2, HuCCA-1, A549 and MOLT-3. The most potent cytotoxic activity against the HepG2, HuCCA-1 and A549 cell lines was found to be m-acetylphenylamino-1,4-naphthoquinone (8) affording IC50 values of 4.758, 2.364 and 12.279 μM, respectively. On the other hand, p-acetylphenylamino-1,4-naphthoquinone (9) exhibited the most potent cytotoxic activity against the MOLT-3 cell line with an IC50 of 2.118 μM. Quantitative structure-activity relationship (QSAR) investigations provided good predictive performance as observed from cross-validated R of 0.9177-0.9753 and RMSE of 0.0614-0.1881. The effects of substituents at the 2-amino position on the naphthoquinone core structure and its corresponding influence on the cytotoxic activity were investigated by virtually constructing additional 1,4-naphthoquinone compounds (13-36) for which cytotoxic activities were predicted using equations obtained from the previously constructed QSAR models. Interpretation of informative descriptors from QSAR models revealed pertinent knowledge on physicochemical properties governing the cytotoxic activities of tested cancer cell lines. It is anticipated that the QSAR models developed herein could provide guidelines for further development of novel and potent anticancer agents. © 2014 Published by Elsevier Masson SAS.
Subject(s)
1,4 naphthoquinone derivative
2 (2 chloro 1,4 dihydro 1,4 dioxonaphthalen 3 ylamino) benzoic acid
2 (3 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (3,4 dimethoxyphenethylamino) 3 chloronaphthalene 1,4 dione
2 (4 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (n butylamino) 3 chloronaphthalene 1,4 dione
2 (n methyl n phenylamino) 3 chloronaphthalene 1,4 dione
2 chloro 3 (phenethylamino)naphthalene 1,4 dione
2 chloro 3 (phenylamino)naphthalene 1,4 dione
2 chloro 3 [[4 (phenylamino)phenyl]amino] naphthalene 1,4 dione
Cytotoxic agent
Doxorubicin
Etoposide
Unclassified drug
1,4 naphthoquinone derivative
2 (2 chloro 1,4 dihydro 1,4 dioxonaphthalen 3 ylamino)benzoic acid
2 (3 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (3,4 dimethoxyphenethylamino) 3 chloronaphthalene 1,4 dione
2 (4 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (n butylamino) 3 chloronaphthalene 1,4 dione
2 (n methyl n phenylamino) 3 chloronaphthalene 1,4 dione
2 chloro 3 (phenethylamino)naphthalene 1,4 dione
2 chloro 3 (phenylamino)naphthalene 1,4 dione
2 chloro 3 (quinolin 8 ylamino)naphthalene 1,4 dione
2 chloro 3 [(4 (phenylamino)phenyl)amino] naphthalene 1,4 dione
Cytotoxic agent
Doxorubicin
Etoposide
Reactive oxygen metabolite
1,4-naphthoquinone
Antineoplastic agent
Naphthoquinone
Antineoplastic activity
Antiproliferative activity
Article
Carbon nuclear magnetic resonance
Drug potency
Drug structure
Drug synthesis
Female
HepG2 cell line
Human
Human cell
IC 50
Lipophilicity
Nucleophilicity
Physical chemistry
Proton nuclear magnetic resonance
Quantitative structure activity relation
Stereospecificity
Substitution reaction
A549 cell line
Alkylation
Article
Base pairing
Cell viability
Concentration response
Controlled study
Dipole
DNA cleavage
DNA damage
DNA denaturation
DNA strand breakage
Drug conformation
Drug cytotoxicity
Electrophilicity
Embryo
Enzyme active site
IC50
Oxidation reduction potential
Validation study
Cell line
Cell proliferation
Chemical structure
Chemistry
Dose response
Drug effects
Drug screening
Synthesis
Antineoplastic Agents
Cell Line
Cell Proliferation
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Molecular Structure
Naphthoquinones
Quantitative Structure-Activity Relationship
2 (2 chloro 1,4 dihydro 1,4 dioxonaphthalen 3 ylamino) benzoic acid
2 (3 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (3,4 dimethoxyphenethylamino) 3 chloronaphthalene 1,4 dione
2 (4 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (n butylamino) 3 chloronaphthalene 1,4 dione
2 (n methyl n phenylamino) 3 chloronaphthalene 1,4 dione
2 chloro 3 (phenethylamino)naphthalene 1,4 dione
2 chloro 3 (phenylamino)naphthalene 1,4 dione
2 chloro 3 [[4 (phenylamino)phenyl]amino] naphthalene 1,4 dione
Cytotoxic agent
Doxorubicin
Etoposide
Unclassified drug
1,4 naphthoquinone derivative
2 (2 chloro 1,4 dihydro 1,4 dioxonaphthalen 3 ylamino)benzoic acid
2 (3 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (3,4 dimethoxyphenethylamino) 3 chloronaphthalene 1,4 dione
2 (4 acetylphenylamino) 3 chloronaphthalene 1,4 dione
2 (n butylamino) 3 chloronaphthalene 1,4 dione
2 (n methyl n phenylamino) 3 chloronaphthalene 1,4 dione
2 chloro 3 (phenethylamino)naphthalene 1,4 dione
2 chloro 3 (phenylamino)naphthalene 1,4 dione
2 chloro 3 (quinolin 8 ylamino)naphthalene 1,4 dione
2 chloro 3 [(4 (phenylamino)phenyl)amino] naphthalene 1,4 dione
Cytotoxic agent
Doxorubicin
Etoposide
Reactive oxygen metabolite
1,4-naphthoquinone
Antineoplastic agent
Naphthoquinone
Antineoplastic activity
Antiproliferative activity
Article
Carbon nuclear magnetic resonance
Drug potency
Drug structure
Drug synthesis
Female
HepG2 cell line
Human
Human cell
IC 50
Lipophilicity
Nucleophilicity
Physical chemistry
Proton nuclear magnetic resonance
Quantitative structure activity relation
Stereospecificity
Substitution reaction
A549 cell line
Alkylation
Article
Base pairing
Cell viability
Concentration response
Controlled study
Dipole
DNA cleavage
DNA damage
DNA denaturation
DNA strand breakage
Drug conformation
Drug cytotoxicity
Electrophilicity
Embryo
Enzyme active site
IC50
Oxidation reduction potential
Validation study
Cell line
Cell proliferation
Chemical structure
Chemistry
Dose response
Drug effects
Drug screening
Synthesis
Antineoplastic Agents
Cell Line
Cell Proliferation
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Molecular Structure
Naphthoquinones
Quantitative Structure-Activity Relationship