Publication: Novel 1,4-naphthoquinone-based sulfonamides: Synthesis, QSAR, anticancer and antimalarial studies
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Issued Date
2015
Resource Type
File Type
application/pdf
ISSN
2235234
Other identifier(s)
2-s2.0-84942155183
Rights Holder(s)
Scopus
Bibliographic Citation
European Journal of Medicinal Chemistry. Vol 103, (2015), p.446-459
Suggested Citation
Pingaew R., Prachayasittikul V., Worachartcheewan A., Nantasenamat C., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Novel 1,4-naphthoquinone-based sulfonamides: Synthesis, QSAR, anticancer and antimalarial studies. European Journal of Medicinal Chemistry. Vol 103, (2015), p.446-459. doi:10.1016/j.ejmech.2015.09.001 Retrieved from: https://hdl.handle.net/20.500.14740/6043
Abstract
A novel series of 1,4-naphthoquinones (33-44) tethered by open and closed chain sulfonamide moieties were designed, synthesized and evaluated for their cytotoxic and antimalarial activities. All quinone-sulfonamide derivatives displayed a broad spectrum of cytotoxic activities against all of the tested cancer cell lines including HuCCA-1, HepG2, A549 and MOLT-3. Most quinones (33-36 and 38-43) exerted higher anticancer activity against HepG2 cell than that of the etoposide. The open chain analogs 36 and 42 were shown to be the most potent compounds. Notably, the restricted sulfonamide analog 38 with 6,7-dimethoxy groups exhibited the most potent antimalarial activity (IC<inf>50</inf> = 2.8 μM). Quantitative structure-activity relationships (QSAR) study was performed to reveal important chemical features governing the biological activities. Five constructed QSAR models provided acceptable predictive performance (R<inf>cv</inf> 0.5647-0.9317 and RMSE<inf>cv</inf> 0.1231-0.2825). Four additional sets of structurally modified compounds were generated in silico (34a-34d, 36a-36k, 40a-40d and 42a-42k) in which their activities were predicted using the constructed QSAR models. A comprehensive discussion of the structure-activity relationships was made and a set of promising compounds (i.e., 33, 36, 38, 42, 36d, 36f, 42e, 42g and 42f) was suggested for further development as anticancer and antimalarial agents. © 2015 Elsevier Masson SAS.
Subject(s)
1,4 naphthoquinone derivative
2 chloro 3 ((3 ((3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
2 chloro 3 ((3 ((6,7 dimethoxy 3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
2 chloro 3 ((4 ((3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
2 chloro 3 ((4 ((6,7 dimethoxy 3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (2 (pyridin 2 yl)ethyl)benzenesulfonamide
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (3,4 dimethoxyphenethyl)benzenesulfonamide
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (pyridin 2 ylmethyl)benzenesulfonamide
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n phenethylbenzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (2 (pyridin 2 yl)ethyl)benzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (3,4 dimethoxyphenethyl)benzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (pyridin 2 ylmethyl)benzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n phenethylbenzenesulfonamide
Etoposide
Sulfonamide
Unclassified drug
1,4-naphthoquinone
Antimalarial agent
Antineoplastic agent
Naphthoquinone
Sulfonamide
A549 cell line
Animal cell
Antimalarial activity
Antineoplastic activity
Article
Biological activity
Computer model
Controlled study
Cytotoxicity
Drug synthesis
HepG2 cell line
Human
Human cell
IC50
Nonhuman
Quantitative structure activity relation
Cell proliferation
Chemical structure
Chemistry
Dose response
Drug effects
Drug screening
Drug sensitivity
Plasmodium falciparum
Quantitative structure activity relation
Synthesis
Tumor cell line
Antimalarials
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Molecular Structure
Naphthoquinones
Parasitic Sensitivity Tests
Plasmodium falciparum
Quantitative Structure-Activity Relationship
Sulfonamides
2 chloro 3 ((3 ((3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
2 chloro 3 ((3 ((6,7 dimethoxy 3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
2 chloro 3 ((4 ((3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
2 chloro 3 ((4 ((6,7 dimethoxy 3,4 dihydroisoquinolin 2(1h) yl)sulfonyl)phenyl)amino)naphthalene 1,4 dione
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (2 (pyridin 2 yl)ethyl)benzenesulfonamide
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (3,4 dimethoxyphenethyl)benzenesulfonamide
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (pyridin 2 ylmethyl)benzenesulfonamide
3 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n phenethylbenzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (2 (pyridin 2 yl)ethyl)benzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (3,4 dimethoxyphenethyl)benzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n (pyridin 2 ylmethyl)benzenesulfonamide
4 ((3 chloro 1,4 dioxo 1,4 dihydronaphthalen 2 yl)amino) n phenethylbenzenesulfonamide
Etoposide
Sulfonamide
Unclassified drug
1,4-naphthoquinone
Antimalarial agent
Antineoplastic agent
Naphthoquinone
Sulfonamide
A549 cell line
Animal cell
Antimalarial activity
Antineoplastic activity
Article
Biological activity
Computer model
Controlled study
Cytotoxicity
Drug synthesis
HepG2 cell line
Human
Human cell
IC50
Nonhuman
Quantitative structure activity relation
Cell proliferation
Chemical structure
Chemistry
Dose response
Drug effects
Drug screening
Drug sensitivity
Plasmodium falciparum
Quantitative structure activity relation
Synthesis
Tumor cell line
Antimalarials
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Molecular Structure
Naphthoquinones
Parasitic Sensitivity Tests
Plasmodium falciparum
Quantitative Structure-Activity Relationship
Sulfonamides