- Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action
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Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2′-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities.
- Parrino, Barbara,Carbone, Anna,Ciancimino, Cristina,Spanò, Virginia,Montalbano, Alessandra,Barraja, Paola,Cirrincione, Girolamo,Diana, Patrizia,Sissi, Claudia,Palumbo, Manlio,Pinato, Odra,Pennati, Marzia,Beretta, Giovanni,Folini, Marco,Matyus, Peter,Balogh, Balázs,Zaffaroni, Nadia
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- Cobalt-Catalyzed Chemoselective Transfer Hydrogenative Cyclization Cascade of Enone-Tethered Aldehydes
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The ligand-free Co-catalyzed chemoselective reductive cyclization cascade of enone-tethered aldehydes with i-PrOH as the environmentally benign hydrogen surrogate is developed by this study. Mechanistic studies disclosed that such a protocol is initiated
- Ma, Shuang-Shuang,Jiang, Biao-Ling,Yu, Zheng-Kun,Zhang, Suo-Jiang,Xu, Bao-Hua
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supporting information
p. 3873 - 3878
(2021/05/26)
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- Ring-Opening/Recyclization Cascades of Monoactivated Cyclopropanes
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A variety of cyclopropyl aryl ketones undergo uncatalyzed cascade ring-opening/recyclization reactions to generate indenones and fluorenones. In addition, a new strategy to access 3-hydroxyindanones possessing two contiguous stereogenic centers, one of th
- Mishra, Uttam K.,Patel, Kaushalendra,Ramasastry, S. S. V.
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supporting information
(2020/05/25)
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- Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals
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The metalloradical activation of o-aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)-carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium-sized ring structures. Herein we make use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical intermediates in the [CoII(TPP)]-catalyzed (TPP=tetraphenylporphyrin) synthesis of two types of 8-membered ring compounds; novel dibenzocyclooctenes and unprecedented monobenzocyclooctadienes. The method was successfully applied to afford a variety of 8-membered ring compounds in good yields and with excellent substituent tolerance. Density functional theory (DFT) calculations and experimental results suggest that the reactions proceed via hydrogen atom transfer from the bis-allylic/benzallylic C?H bond to the carbene radical, followed by two divergent processes for ring-closure to the two different types of 8-membered ring products. While the dibenzocyclooctenes are most likely formed by dissociation of o-quinodimethanes (o-QDMs) which undergo a non-catalyzed 8π-cyclization, DFT calculations suggest that ring-closure to the monobenzocyclooctadienes involves a radical-rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring-closure reactions to chiral monobenzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt-porphyrin catalyst.
- Lankelma, Marianne,Zhou, Minghui,de Bruin, Bas,van der Vlugt, Jarl Ivar
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supporting information
p. 11073 - 11079
(2020/04/29)
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- Assessment of the regioselectivity in the condensation reaction of unsymmetrical o-phthaldialdehydes with alanine
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One approach for the synthesis of isoindolinones, a privileged bioactive heterocyclic core structure, involves a condensation reaction of o-phthaldialdehydes with a suitable nitrogen-containing nucleophile. This fascinating reaction is revisited here in the context of the use of o-phthaldialdehydes that contain additional substituents in the aromatic ring leading to a detailed analysis of the regioselectivity of the reaction. Eleven monosubstituted o-phthaldialdehydes were synthesised and reacted with alanine. The regioselectivity observed across the eleven substrates led to the design of a disubstituted substrate that reacted with very high control. A gram-scale reaction followed by esterification gave one major regioisomer in high yield. In addition, the regioselectivity observed on reaction of two novel monodeuterated substrates led to an increased mechanistic understanding.
- D'Hollander, Agathe C.A.,Westwood, Nicholas J.
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supporting information
p. 224 - 239
(2017/12/08)
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- Catalytic Dibenzocyclooctene Synthesis via Cobalt(III)–Carbene Radical and ortho-Quinodimethane Intermediates
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The metalloradical activation of ortho-benzallylaryl N-tosyl hydrazones with [Co(TPP)] (TPP=tetraphenylporphyrin) as the catalyst enabled the controlled exploitation of the single-electron reactivity of the redox non-innocent carbene intermediate. This method offers a novel route to prepare eight-membered rings, using base metal catalysis to construct a series of unique dibenzocyclooctenes through selective Ccarbene?Caryl cyclization. The desired eight-membered-ring products were obtained in good to excellent yields. A large variety of aromatic substituents are tolerated. The proposed reaction mechanism involves intramolecular hydrogen atom transfer (HAT) to CoIII–carbene radical intermediates followed by dissociation of an ortho-quinodimethane that undergoes 8π cyclization. The mechanism is supported by DFT calculations, and the presence of radical-type intermediates was confirmed by trapping experiments.
- te Grotenhuis, Colet,van den Heuvel, Naudin,van der Vlugt, Jarl Ivar,de Bruin, Bas
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supporting information
p. 140 - 145
(2017/12/13)
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- Enantioselective N-Heterocyclic Carbene Catalysis by the Umpolung of α,β-Unsaturated Ketones
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N-Heterocyclic carbene-catalyzed formation of β-anionic intermediates from enones has been employed in the enantioselective synthesis of 2-aryl propionates. The reaction was achievable using a homochiral 4-MeOC6H4 morpholinone cataly
- Nakano, Yuji,Lupton, David W.
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supporting information
p. 3135 - 3139
(2016/03/12)
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- NHC-catalyzed oxidative cyclization reaction for the synthesis of 3-substituted phthalides
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An efficient NHC-catalyzed domino oxidation/oxa-Michael addition reaction of 2-alkenylbenzaldehydes has been developed to afford 3-substituted phthalides bearing a C3-stereogenic center with a broad substrate scope and wide functional group tolerance. The preliminary results of the asymmetric process have been provided as well. the Partner Organisations 2014.
- Youn, So Won,Song, Hyoung Sub,Park, Jong Hyub
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supporting information
p. 2388 - 2393
(2014/04/03)
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- Organocatalytic, Enantioselective, intramolecular oxa-michael reaction of alkoxyboronate: A new strategy for enantioenriched 1-substituted 1,3-Dihydroisobenzofurans
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An unprecedented strategy for the synthesis of enantioenriched 1-substituted 1,3-dihydroisobenzofurans via an enantioselective oxa-Michael reaction of o-alkoxyboronate containing chalcone (II) has been accomplished employing cinchona alkaloid based squara
- Ravindra, Barnala,Das, Braja Gopal,Ghorai, Prasanta
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supporting information
p. 5580 - 5583
(2015/02/19)
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- One-pot syntheses of isoquinolin-3-ones and benzo-1,4-diazepin-2,5-diones utilizing Ugi-4CR post-transformation strategy
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One-pot and efficient syntheses of structurally diverse isoquinolin-3-ones and isoquinolin-3-one-based benzo-1,4-diazepin-2,5-diones have been developed. The notable features of the process include the Ugi condensation of monomasked phthalaldehydes with a
- Che, Chao,Li, Song,Yu, Zhixiong,Li, Fangfang,Xin, Shengchang,Zhou, Liyan,Lin, Shuo,Yang, Zhen
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supporting information
p. 202 - 207
(2013/05/09)
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- Efficient synthesis of selected phthalazine derivatives
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Four phthalazine derivatives have been prepared from substituted 2-bromobenzaldehyde acetals by a sequence involving: (1) lithiation and formylation; (2) deprotection; and (3) condensative cyclization with hydrazine. Two additional phthalazines were prepa
- Bunce, Richard A.,Harrison, Todd,Nammalwar, Baskar
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p. 123 - 126
(2013/01/16)
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- NHC-catalyzed spiro bis-indane formation via domino stetter - Aldol - Michael and stetter - Aldol - Aldol reactions
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Two novel domino NHC-catalyzed spirocyclizations are described herein, enabling the rapid construction of three new carbon - carbon bonds and a quaternary center with high diastereoselectivity. A variety of spiro bis-indane structures are assembled in a single step from simple o-phthaldialdehyde derivatives.
- Sanchez-Larios, Eduardo,Holmes, Janice M.,Daschner, Crystal L.,Gravel, Michel
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supporting information; experimental part
p. 5772 - 5775
(2011/03/22)
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- Metal-catalyzed cycloisomerization of enyne functionalities via a 1,3-alkylidene migration
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We report a new metal-catalyzed 6-endo-dig cyclization of cis-4,6-dien-1-yn-3-ols, which produces substituted benzene and naphthalene derivatives with structural reorganization. In this process, we observe a 1,3-alkylidene migration via cleavage of the olefin double bond of the starting substrates. The ease and reliability of this cyclization are manifested by its compatibility with a wide array of diverse substrates and several π-alkyne activators, including PtCl2, Zn(OTf)2, AuCl, and AuCl3. Copyright
- Lin, Ming-Yuan,Das, Arindam,Liu, Rai-Shung
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p. 9340 - 9341
(2007/10/03)
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- A convenient access to benzo-substituted phthalazines as potential precursors to DNA intercalators
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2-Nitro-5-methoxybenzaldehyde is converted to amines 2 and 7 via two alternative routes. Upon diazotisation and Sandmeyer reaction, halides 4 and 9 are formed, which, through lithiation and formylation lead to the o-phthalaldehyde. Further cyclisation with hydrazine gives the 5-methoxy-substituted phthalazine.
- Tsoungas, Petros G,Searcey, Mark
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p. 6589 - 6592
(2007/10/03)
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- Iminium ion-mediated cyclizations of 4-aryl-1,4-dihydropyridines. Alternate cyclization pathways
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Acid-catalyzed cyclization of dimethyl 2,6-dimethyl-4--1,4-dihydropyridine-3,5-dicarboxylate affords novel products via competing intramolecular processes.The present mechanistic pathways differ from previous iminium ion-media
- Hartman, George D.,Halczenko, Wasyl,Cochran, David W.
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p. 556 - 559
(2007/10/02)
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- Facile Intramolecular Tosylhydrazone-Mediated Cyclopropanation Reactions of 4-(2-Formylphenyl)-1,4-dihydropyridines
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Hantzsch-type 4-(2-formylphenyl)-1,4-dihydropyridine derivatives 4-7 undergo facile intramolecular tosylhydrazone-mediated cyclopropanation reactions to afford the highly constrained analogues 16-19, respectively.Prior formation of the conjugate anions of
- Remy, David C.,King, Stella W.,Cochran, David,Springer, James P.,Hirshfield, Jordon
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p. 4120 - 4125
(2007/10/02)
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