Abstract
To define the SAR, a series of novel N-arylsulfonylimidazolidinone derivatives were evaluated for their in vitro anticancer activity against five human tumor cell lines, including A549, COLO205, KATO III, K562, SK-OV-3 and murine leukemia (P288D1) cell line. Among them, N-(2-chloroacetyl)-6-(2-oxo-4-phenylimidazolidin-1-ylsulfonyl)-3,4-dihydroquinoline-1(2H)-carboxamide (4m) and N-cyclohexyl-6-(2-oxo-4-phenylimidazolidin-1-ylsulfonyl)-3,4-dihydroquinoline-1(2H)-carboxamide (4n) exhibited comparable in vitro anticancer activity to doxorubicin against A549, KATO III and K562 cell lines and gave superior xenographic results against NCI-H23 and SW620 cancer cell lines. Regarding the structure-activity relationship, two critical points were discovered; the steric congestion at 4-position of N-arylsulfonylimidazolidinone scaffold abolishes the activity and the bulkiness or hydrophobicity of acyl groups at 3,4-dihydroquinoline of 4, especially with carbamoyl moiety, enormously enhances the activity.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Arylsulfonates / chemical synthesis
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Arylsulfonates / chemistry
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Arylsulfonates / pharmacology*
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Cell Line, Tumor
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Cell Survival / drug effects
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / pathology
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Doxorubicin / pharmacology
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Drug Screening Assays, Antitumor
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Female
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Humans
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Hydrophobic and Hydrophilic Interactions
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Imidazolidines / chemical synthesis
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Imidazolidines / chemistry
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Imidazolidines / pharmacology*
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / pathology
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Mice
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Mice, Nude
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Molecular Conformation
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Neoplasm Transplantation
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / pathology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Arylsulfonates
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Imidazolidines
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N-(2-chloroacetyl)-6-(2-oxo-4-phenylimidazolidin-1-ylsulfonyl)-3,4-dihydroquinoline-1(2H)-carboxamide
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N-cyclohexyl-6-(2-oxo-4-phenylimidazolidin-1-ylsulfonyl)-3,4-dihydroquinoline-1(2H)-carboxamide
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Doxorubicin