- Activation of Phenyl 4-(2-Oxo-3-Alkylimidazolidin-1-yl)benzenesulfonates Prodrugs by CYP1A1 as New Antimitotics Targeting Breast Cancer Cells
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Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation, and mechanism of action of phenyl 4-(2-oxo-3-Alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) that are antimicrotubule prodrugs activated by CYP1A1. Although PAIB-SOs are inert in most cells tested, they are highly cytocidal toward several human breast cancer cells, including hormone-independent and chemoresistant types. PAIB-SOs are N-dealkylated into cytotoxic phenyl 4-(2-oxo-3-imidazolidin-1-yl)benzenesulfonates (PIB-SOs) in CYP1A1-positive cancer cells, both in vitro and in vivo. In conclusion, PAIB-SOs are novel chemotherapeutic prodrugs with no equivalent among current antineoplastics and whose selective action toward breast cancer is tailored to the characteristic pattern of CYP1A1 expression observed in a large percentage of human breast tumors.
- Fortin, Sébastien,Charest-Morin, Xavier,Turcotte, Vanessa,Lauvaux, Coraline,Lacroix, Jacques,C?té, Marie-France,Gobeil, Stéphane,Gaudreault, René C.
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p. 4963 - 4982
(2017/06/28)
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- SUBSTITUTED 2-IMIDAZOLIDONES AND ANALOGS
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Compounds of formula (I): wherein R1, R2, R3, R4, R7, R6, R7, R8, R9, A, X and Y as defined herein are provided as useful for the treatment of cancer or for
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Page/Page column 27-28; 107
(2011/09/19)
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- Lithiation of 1-arylimidazol-2(1H)-ones and 1-aryl-4,5-dihydroimidazol- 2(1H)-ones
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1-Arylimidazol-2(1H)-ones are shown to be readily lithiated, using 2 mol equiv. of n-butyllithium, on the benzene ring, ortho to the heterocycle. 1-Aryl-4,5-dihydroimidazol-2(1H)-ones also undergo metalation on the aromatic substitutuent ortho to the heterocycle, but less efficiently. 1-Aryl-3-methylimidazol-2(1H)-ones are lithiated on the heterocyclic ring and then on the benzene ring ortho to the heterocycle. No ortho-directing effect was found for 1-aryl-4,5-dihydro-3-methylimidazol-2(1H)-ones.
- Llopart, Carme Cantos,Ferrer, Conchita,Joule, John A.
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p. 1649 - 1661
(2007/10/03)
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- Investigation of the Mitsunobu reaction of N-(2-hydroxyethyl)-N'- phenyl-ureas
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The Mitsunobu reaction of N-(2-hydroxyethyl)-ureas 1 using PPh3 and EtO2CN=NCO2Et led to the mixture of N- and O-alkylation products or a single isomer depending on the substrates.
- Kim, Taek Hyeon,Lee, Gue-Jae,Cha, Mi-Hyun
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p. 2753 - 2758
(2007/10/03)
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- Human β3 adrenergic receptor agonists containing imidazolidinone and imidazolone benzenesulfonamides
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The cyclopentylpropylimidazolidinone L-766,892 is a potent β3 AR agonist (EC50 5.7 nM, 64% activation) with 420- and 130-fold selectivity over binding to the β1 and β2 ARs, respectively. In anesthetized rhesus monkeys, L-766,892 elicited dose-dependent hyperglycerolemia (ED50 0.1 mg/kg) with minimal effects on heart rate.
- Naylor, Elizabeth M.,Parmee, Emma R.,Colandrea, Vincent J.,Perkins, Leroy,Brockunier, Linda,Candelore, Mari R.,Cascieri, Margaret A.,Colwell Jr., Lawrence F.,Deng, Liping,Feeney, William P.,Forrest, Michael J.,Hom, Gary J.,MacIntyre, D. Euan,Strader, Catherine D.,Tota, Laurie,Wang, Pei-Ran,Wyvratt, Matthew J.,Fisher, Michael H.,Weber, Ann E.
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p. 755 - 758
(2007/10/03)
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