- Dynamic Kinetic Asymmetric Transformation of Racemic Diastereomers: Diastereo- and Enantioconvergent Michael–Henry Reactions to Afford Spirooxindoles Bearing Furan-Fused Rings
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Dynamic kinetic asymmetric transformation (DYKAT) reactions of racemic diastereomer mixtures that afford the products as essentially single diastereomers with high enantioselectivities are described. We demonstrated the DYKAT in the diastereo- and enantio
- Sohail, Muhammad,Tanaka, Fujie
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supporting information
p. 21256 - 21260
(2021/08/23)
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- Organocatalytic Asymmetric Synthesis of Aza-Spirooxindoles via Michael/Friedel-Crafts Cascade Reaction of 1,3-Nitroenynes and 3-Pyrrolyloxindoles
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An asymmetric [3+3] cyclization of nitroenynes and 3-pyrrolyloxindoles has been realized with a chiral bifunctional squaramide catalyst. This Michael/Friedel-Crafts cascade strategy provides a facile and efficient access to enantioenriched polycyclic aza-spirooxindoles with 32-95% isolated yields and excellent stereocontrol under mild reaction conditions.
- Ni, Qijian,Wang, Xuyang,Zeng, Da,Wu, Qianling,Song, Xiaoxiao
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supporting information
p. 2273 - 2278
(2021/04/05)
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- Microwave-assisted synthesis and antimicrobial activity of novel spiro 1,3,4-thiadiazolines from isatin derivatives
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This work describes the synthesis of spiro 1,3,4-thiadiazolines from isatin-β-thiosemicarbazone acetylation, using microwave irradiation as a source of heating the reaction medium. N-substituted isatin derivatives were used as substrates to obtain thiosemicarbazones by adding thiosemicarbazide to the isatin ketone carbonyl. The final synthetic step was the reaction of thiosemicarbazones with acetic anhydride under microwave irradiation to get the spiro compounds. Reaction times ranged from 6 to 18 minutes resulting in yields of up to 90%. Biological assays have shown promising antibacterial and antifungal activity, especially spiro thiadiazolines derived from allylated isatins. All the proposed molecules proved to be potential drug candidates based on the results of the in silico investigation, with satisfactory drug-likeness and drug-score, respecting Lipinski's rule. The use of the microwave reactor was efficient for the synthesis of thiosemicarbazones and spiro compounds, resulting in a significant reduction in reaction times with conventional heating. Taking into account the threat of antimicrobial resistance, this work presents a series of bioactive molecules that are easily obtained via microwave reaction.
- da Costa, Daniel Pereira,de Castro, Aleff Cruz,da Silva, Girlyanderson Araújo,Lima-Junior, Claudio Gabriel,de Andrade Júnior, Francisco Patricio,de Oliveira Lima, Edeltrudes,Vaz, Boniek Gontijo,da Silva, Lidya Cardoso
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p. 766 - 776
(2020/12/31)
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- Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations
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In the current medical era, human health is experiencing numerous challenges, particularly the human malignancies. Therefore, the therapeutic arsenal for these malignancies is to be inexorably enhanced with new treatments that target tumor cells in a selective manner. In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. The large tricyclic TBI motif is anticipated to achieve a plethora of hydrophobic interactions within the CDK2 binding site. The growth of the two examined cell lines was significantly inhibited by most the prepared hybrids with IC50 ranges; (2.60 ± 1.47–20.90 ± 1.17 μM, against MDA-MB-231) and (1.27 ± 0.06–16.83 ± 0.95 μM, against MCF-7). In particular, hybrids 7a, 7d and 10a displayed potent dual activity against the examined cell lines, and thus selected for further investigations. They exerted a significance alteration in the cell cycle progression, in addition to an apoptosis induction within both MDA-MB-231 and MCF-7 cells. Furthermore, 7a, 7d and 10a displayed potent CDK2 inhibitory action (IC50 = 96.46 ± 5.3, 26.24 ± 1.4 and 42.95 ± 2.3 nM, respectively). The docking simulations unveiled, as expected, the ability of the TBI ring to well-accommodate and establish several hydrophobic interactions within a hydrophobic pocket in the CDK2 binding site. Also, the docking simulations highlighted the significance of incorporation of the hydrazide linker and isatin unsubstituted (NH) functionality in the H-bonding interactions. Interestingly, the most potent CDK2 inhibitor 7d achieved the best binding score (-11.2 Kcal/mole) and formed the most stable complex with CDK2 enzyme (RMSD = 1.24 ?) in a 100 ns MD simulation. In addition, the MM-PBSA calculations ascribed the lowest binding free energy to the 7d–CDK2 complex (?323.69 ± 15.17 kJ/mol). This could be attributed to an incorporation of the 5-OCH3 group that was engaged in an extra hydrogen bonding with key THR14 amino acid residue. Finally, these results suggested hybrid 7d as a good candidate for further optimization as promising breast cancer antitumor agent and CDK2 inhibitor.
- Eldehna, Wagdy M.,El Hassab, Mahmoud A.,Abo-Ashour, Mahmoud F.,Al-Warhi, Tarfah,Elaasser, Mahmoud M.,Safwat, Nesreen A.,Suliman, Howayda,Ahmed, Marwa F.,Al-Rashood, Sara T.,Abdel-Aziz, Hatem A.,El-Haggar, Radwan
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supporting information
(2021/03/15)
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- Applications of Ytterbium(II) Reagent as Grignard Reagent and Single-Electron Transfer Reagent in the Synthesis of 3-Substituted 2-Oxindoles
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The use of ytterbium(II) reagent as both nucleophilic reagent and single-electron transfer reagent in the reaction of isatin derivatives with ytterbium(II) reagent is reported. From a synthetic point of view, a general, efficient, and experimentally simple one-pot method for the preparation of 3-substituted 2-oxindoles was developed.
- Wang, Pengkai,Cao, Xuyan,Zhang, Songlin
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supporting information
p. 3836 - 3846
(2021/07/02)
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- Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies
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The serine/threonine protein kinases CDK2 and GSK-3β are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3β inhibitors targeting breast cancer (5a–g, 7a–h, and 13a–b). The N1 -unsubstituted oxindole derivatives, series 5, showed moderate to potent activity on both MCF-7 and T-47D breast cancer cell lines. Compounds 5d–f showed the most potent cytotoxic activity with IC50 of 3.41, 3.45 and 2.27 μM, respectively, on MCF-7 and of 3.82, 4.53 and 7.80 μM, respectively, on T-47D cell lines, in comparison to the used reference standard (staurosporine) IC50 of 4.81 and 4.34 μM, respectively. On the other hand, the N1 -substituted oxindole derivatives, series 7 and 13, showed moderate to weak cytotoxic activity on both breast cancer cell lines. CDK2 and GSK-3β enzyme inhibition assay of series 5 revealed that compounds 5d and 5f are showing potent dual CDK2/GSK-3β inhibitory activity with IC50 of 37.77 and 52.75 nM, respectively, on CDK2 and 32.09 and 40.13 nM, respectively, on GSK-3β. The most potent compounds 5d–f caused cell cycle arrest in the G2/M phase in MCF-7 cells inducing cell apoptosis because of the CDK2/GSK-3β inhibition. Molecular docking studies showed that the newly synthesised N1 -unsubstituted oxindole hybrids have comparable binding patterns in both CDK2 and GSK-3β. The oxindole ring is accommodated in the hinge region interacting through hydrogen bonding with the backbone CO and NH of the key amino acids Glu81 and Leu83, respectively, in CDK2 and Asp133 and Val135, respectively, in GSK-3β. Whereas, in series 7 and 13, the N1 -substitutions on the oxindole nucleus hinder the compounds from achieving these key interactions with hinge region amino acids what rationalises their moderate to low anti-proliferative activity.
- Eldehna, Wagdy M.,Al-Rashood, Sara T.,Al-Warhi, Tarfah,Eskandrani, Razan O.,Alharbi, Amal,El Kerdawy, Ahmed M.
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p. 270 - 285
(2020/12/18)
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- Organocatalytic Enantioselective Synthesis of Tetrahydro-Furanyl Spirooxindoles via [3+2] Annulations of 3-Hydroxyoxindoles and Cyclic Ketolactams
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Asymmetric construction of pharmacologically interesting tetrahydrofuranyl spirooxindole frameworks has been achieved through organocatalytic [3+2] annulations of the readily available 3-hydroxyoxindoles and pyrrolidone-derived cyclic ketolactams. A variety of chiral spiro tetrahydrofuranyl products, which contain four contiguous stereocenters including two tetrasubstituted carbon centers, have been rapidly synthesized with remarkable results (up to 99% yield, >95:5 dr, and 99:1 er). Synthetic derivatization of the hemiketal moiety enables the installation of various halogen atoms into the structurally complex molecules in a stereospecific manner. Preliminary screening of anticancer bioactivity was performed, and 4 w showed obvious inhibitory capacity to the proliferation on a panel of cancer cell lines. (Figure presented.).
- Liu, Yue,Zhang, Ying,Huang, Qian-Wei,Gou, Chuan,Li, Qing-Zhu,Dai, Qing-Song,Leng, Hai-Jun,Li, Jun-Long
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supporting information
p. 2177 - 2182
(2021/03/08)
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- Palladium catalyzed divergent cycloadditions of vinylidenecyclopropane-diesters with methyleneindolinones enabled by zwitterionic π-propargyl palladium species
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A palladium-catalyzed divergent synthesis of spirooxindoles fused with a five- or a six-membered ring by a cycloaddition reaction of vinylidenecyclopropane-diesters with methyleneindolinones was disclosed. This protocol features anin situgenerated unprecedented zwitterionic π-propargyl palladium species in cycloaddition reactions and a switchable process between (3+2) and (4+2) cycloadditions by changing the phosphine ligand.
- Niu, Ben,Wei, Yin,Shi, Min
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supporting information
p. 4783 - 4786
(2021/05/25)
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- Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer
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In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (5a–e and 7a–i) was designed and synthesised. The anticancer activity for compounds (5b–d, 7a, 7b, 7d and 7g) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates (5a–e and 7a–i) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC50 = 8.7 and 9.4 μM (5a), and 6.5 and 9.8 μM for (5d), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis.
- Eldehna, Wagdy M.,Salem, Rofaida,Elsayed, Zainab M.,Al-Warhi, Tarfah,Knany, Hamada R.,Ayyad, Rezk R.,Traiki, Thamer Bin,Abdulla, Maha-Hamadien,Ahmad, Rehan,Abdel-Aziz, Hatem A.,El-Haggar, Radwan
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p. 1424 - 1435
(2021/07/02)
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- Catalytic Asymmetric Halogenation/Semipinacol Rearrangement of 3-Hydroxyl-3-vinyl Oxindoles: A Stereodivergent Kinetic Resolution Process
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A highly enantioselective halogenation/semipinacol rearrangement of isatin-derived allylic alcohols has been developed with a chiral N,N′-dioxide/ScIII complex as catalyst. This strategy involved a pivotal stereodivergent kinetic resolution process and provided a facile and efficient entry to optically active halo-substituted quinolone derivatives and quinoline alkaloids with a quaternary stereocenter simultaneously under mild reaction conditions. Based on the control experiments together with kinetic studies and DFT calculations, a possible catalytic cycle was proposed to illustrate the reaction process and enantiocontrol.
- Cao, Weidi,Dai, Li,Feng, Xiaoming,Hu, Xinyue,Liu, Wen,Zeng, Zi,Zhou, Yuqiao
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supporting information
p. 26599 - 26603
(2021/11/16)
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- Accessing New 5-α-(3,3-Disubstituted Oxindole)-Benzylamine Derivatives from Isatin: Stereoselective Organocatalytic Three Component Petasis Reaction
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A one-step, three-component Petasis reaction of isatin derived 5-arylboronate-3-substituted oxindole derivatives with salicylaldehydes and secondary amines affords new enantiomerically pure structurally diverse 5-α-(3-substituted-oxindole)-benzylamine derivatives. The reaction shows good substrate and reagent scope affording the products with good to excellent yields (up to >99 % yield) and enantioselectivities (up to 99 % ee) using cheap and readily available (R)-BINOL as the organocatalyst. A diastereoselective version of the reaction was also developed where moderate yields (37 to 55 % yield), excellent enantioselectivities (up to 99 % ee) and good diastereoselectivities (up to 86 % de) were obtained for new 5-α-(3-hydroxy-oxindole)-benzylamine derivatives, having two stereocenters. The reaction is also feasible on gram-scale.
- Burke, Anthony J.,Erxleben, Andrea,Marques, Carolina S.,McArdle, Patrick
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- Carbene-Catalyzed Enantioselective Aromatic N-Nucleophilic Addition of Heteroarenes to Ketones
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The aromatic nitrogen atoms of heteroarylaldehydes are activated by carbene catalysts to react with ketone electrophiles. Multi-functionalized cyclic N,O-acetal products are afforded in good to excellent yields and optical purities. Our reaction involves the formation of an unprecedented aza-fulvene-type acylazolium intermediate. A broad range of N-heteroaromatic aldehydes and electron-deficient ketone substrates works effectively in this transformation. Several of the chiral N,O-acetal products afforded through this protocol exhibit excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichemicals for plant protection.
- Liu, Yonggui,Luo, Guoyong,Yang, Xing,Jiang, Shichun,Xue, Wei,Chi, Yonggui Robin,Jin, Zhichao
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supporting information
p. 442 - 448
(2019/11/25)
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- Candida antarctica lipase-B-catalyzed kinetic resolution of 1,3-dialkyl-3-hydroxymethyl oxindoles
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Candida antarctica (CAL-B) lipase-catalyzed resolution of 1,3-dialkyl-3-hydroxymethyl oxindoles has been performed to obtain (R)-1,3-dialkyl-3-acetoxymethyl oxindoles with up to 99% ee and (S)-1,3-dialkyl-3-hydroxymethyl oxindoles with up to 78% ee using vinyl acetate as acylating agent and acetonitrile as solvent transforming (S)-3-allyl-3-hydroxymethyl oxindole to (3S)-1′-benzyl-5-(iodomethyl)-4,5-dihydro-2H-spiro[furan-3,3′-indolin]-2′-one. The optically active 3-substituted-3-hydroxymethyl oxindoles and spiro-oxindoles are among the key synthons in the synthesis of potentially biologically active molecules.
- Kumar, Naveen,Kumar, Akshay,Sahoo, Subash Chandra,Chimni, Swapandeep Singh
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supporting information
p. 1377 - 1394
(2020/11/23)
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- Facile synthesis of isatins by direct oxidation of indoles and 3-iodoindoles using NIS/IBX
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A facile one-pot access to a broad range of isatins by direct oxidation of indoles using NIS/IBX reagent in DMSO at 25 °C in very good isolated yields is reported. It is shown by mechanistic investigations that a number of substituted indoles react rapidly with NIS in DMSO to produce intermediary 3-iodoindoles, which undergo oxidation subsequently to isatins with IBX.
- Chandra, Ajeet,Yadav, Navin R.,Moorthy, Jarugu Narasimha
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supporting information
p. 2169 - 2174
(2019/03/04)
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- Synthesis and anticancer activity evaluation of azepinobisindoles;the isomeric iheyamine A-derivatives
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Azepinobisindole derivatives, the isomeric Iheyamine skeleton, were prepared and their anticancer activity evaluation were investigated against two human cancer cell lines, Hepatocellular carcinoma (HepG2) and human cervical cancer line (HeLa) as well as the normal cell line (Vero cell line) using MTT assay. The anticancer activity results indicated that 2-methoxy-5-methyl-5H-azepino[2,3-b:4,5-b]diindole was the most active derivative against tested cell lines. Additionally, molecular docking study in silico the possible inhibitory effect of cyclin-dependent kinase 2 (CDK2) by the azepinoindole revealed that all synthesized compounds fit well in the binding cavity of CDK2.
- Phutdhawong, Weerachai,Rattanopas, Sopita,Sirirak, Jitnapa,Taechowisan, Thongchai,Phutdhawong, Waya S.
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p. 723 - 731
(2019/06/07)
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- Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents
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Herein we report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids (6a-f and 9a-l). A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111 in a single chemical framework. As planned, a substantial improvement of inhibitory profile of the target hybrids (KIs: 4.7–86.1 nM) towards hCA IX in comparison to N-unsubstituted leads IVa-c (KIs: 192–239 nM), was achieved. Molecular docking of the designed hybrids in CA IX active site unveiled, as planned, the ability of N-alkylated and N-benzylated isatin moieties to accommodate in a wide hydrophobic pocket formed by T73, P75, P76, L91, L123 and A128, establishing strong van der Waals interactions. Hybrid 6c displayed good anti-proliferative activity under hypoxic conditions towards breast cancer MDA-MB-231 and MCF-7 cell lines (IC50 = 7.43 ± 0.28 and 12.90 ± 0.34 μM, respectively). Also, 6c disrupted the MDA-MB-231 cell cycle via alteration of the Sub-G1 phase and arrest of G2-M stage. Additionally, 6c displayed significant increase in the percent of annexinV-FITC positive apoptotic cells from 1.03 to 18.54%. Furthermore, 6c displayed potent VEGFR-2 inhibitory activity (IC50 = 260.64 nM). Collectively, these data suggest 6c as a promising lead molecule for the development of effective anticancer agents.
- Eldehna, Wagdy M.,Abo-Ashour, Mahmoud F.,Nocentini, Alessio,El-Haggar, Radwan S.,Bua, Silvia,Bonardi, Alessandro,Al-Rashood, Sara T.,Hassan, Ghada S.,Gratteri, Paola,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
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p. 147 - 160
(2018/11/23)
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- Click-chemistry approach to synthesis of functionalized isatin-ferrocenes and their biological evaluation against the human pathogen Trichomonas vaginalis
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Copper-promoted azide-alkyne cycloadditions were attempted to synthesize a series of variedly functionalized 1H-1,2,3-triazole-linked isatin-ferrocene, ferrocenylmethoxy-isatin and isatin-ferrocenyl-chalcone conjugates. The synthesized scaffolds were assayed for their inhibitory activity against T. vaginalis as well as several common normal human flora bacteria. The observed inhibitory activities against T. vaginalis and undetectable inhibition of microflora bacteria suggest that these compounds may be specific against trichomonad protozoa and could serve as a new scaffold for synthesis of novel compounds against this important human pathogen.
- Singh, Amandeep,Zhang, David,Tam, Christina C.,Cheng, Luisa W.,Land, Kirkwood M.,Kumar, Vipan
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- 3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights
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Herein we describe the design and synthesis of two series of sulfonamides featuring N-unsubstituted (4a-c) or N-substituted (7a-o) isatin moieties (as tails) connected to benzenesulfonamide moiety via a hydrazine linker. All the prepared sulfonamides (4a-c and 7a-o) showed potent inhibitory activities toward transmembrane tumor-associated human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, IX and XII with KI range (8.3–65.4 nM) and (11.9–72.9 nM), respectively. Furthermore, six sulfonamides (7e, 7i, 7j, 7m, 7n and 7o) were assessed for their anti-proliferative activity, according to US-NCI protocol, toward a panel of sixty cancer cell lines. Compounds 7j and 7n were the most promising counterparts in this assay displaying broad spectrum anti-proliferative activity toward diverse cell lines. Also, sulfonamide 7n significantly inhibited clonogenicity of HCT-116 cells in a concentration dependent manner in the colony forming assay. Moreover, molecular modeling studies were performed to gain insights for the plausible binding interactions and affinities for the target isatin-based sulfonamides (4a-c and 7a-o) within hCA isoforms II and IX active sites.
- Abo-Ashour, Mahmoud F.,Eldehna, Wagdy M.,Nocentini, Alessio,Bonardi, Alessandro,Bua, Silvia,Ibrahim, Hany S.,Elaasser, Mahmoud M.,Kry?tof, Vladimír,Jorda, Radek,Gratteri, Paola,Abou-Seri, Sahar M.,Supuran, Claudiu T.
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- Asymmetric Conjugate Addition of Ethylene Sulfonyl Fluorides to 3-Amido-2-oxindoles: Synthesis of Chiral Spirocyclic Oxindole Sultams
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An enantioselective conjugate addition of ethylene sulfonyl fluorides to 3-amido-2-oxindoles has been developed. Quinine-derived squaramides were identified as efficient catalysts. A series of spirocyclic oxindole sultams were prepared with excellent yields and enantioselectivities. A reaction mechanism via bifunctional activation was proposed.
- Chen, Jie,Huang, Bao-Qin,Wang, Zeng-Qing,Zhang, Xue-Jing,Yan, Ming
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supporting information
p. 9742 - 9746
(2019/11/28)
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- Synthesis of novel class of n-alkyl-isatin-3-iminobenzoic acid derivatives and their biological activity in zebrafish embryos and human cancer cell lines
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Isatin (1H-indole-2,3-dione) and many of its derivatives are reported to have pharmacological properties. In this study, we report the synthesis and biological activity of a new class of N-alkyl-isatin-3-iminoben-zoic acid derivatives prepared via the condensation of N-alkyl isatin with 4-aminobenzoic acid by conventional, microwave, and ultrasonic methods. Microwave irradiation yielded the products in a shorter reaction time with higher yields and purities. The compounds were screened in zebrafish embryos, and also in three human cancer cell lines (MCF7, HepG2, and Jurkat) and one normal human cell line i.e., human foreskin cell line (HFF-1). Two compounds (3c, 3f) were found to be highly effective against hematopoiesis in live zebrafish embryo at 10μM concentration. The developmental stage-dependent treatment indicated that these compounds interfered with the differentiation of hemangioblasts to hematopoietic cells in zebrafish embryos. The comparative screening of semaxanib (SU5416) (a known isatin derivatives), to compounds synthesized in this study, revealed the contrasting effects of these two classes of isatin derivatives on zebrafish hematopoiesis. Most of the N-alkyl-isatin-3-iminobenzoic acid derivatives were toxic on cancer and non-cancer tested human cells lines, however, the compounds 3c and 3f specifically affected the cell viability of Jurkat cells (human hematological cell line) with least IC50 values of 16.5 and 7.8μM. The structure–activity relationship (SAR) analysis indicated that the substitution pattern of the isatin at the 5-position was vital for activity. The in vivo and in vitro biological activities of these compounds suggested their potential use as pharmaceutical compounds for human leukemia treatment.
- Farooq, Muhammad,Al Marhoon, Zainab Mohammed,Taha, Nael Abu,Baabbad, Almohannad Abdulrahman,Al-Wadaan, Mohammed Ahmed,El-Faham, Ayman
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p. 350 - 359
(2018/03/22)
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- Cinchona-alkaloid-catalyzed enantioselective hydroxymethylation of 3-fluorooxindoles with paraformaldehyde
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Cinchona-alkaloid-catalyzed hydroxymethylation of 3-fluorooxindoles using paraformaldehyde as the C1 unit was achieved. A wide range of 3-fluorooxindoles was successfully reacted to give the corresponding 3-fluoro-3-hydroxymethyloxindoles with high efficiency and moderate to good enantioselectivity.
- Zhao, Jian-bo,Ren, Xinfeng,Zheng, Bu-quan,Ji, Jian,Qiu, Zi-bin,Li, Ya
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supporting information
p. 44 - 51
(2018/10/02)
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- A C=O???Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols
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A combination of experimental and computational studies have identified a C=O???isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.
- Greenhalgh, Mark D.,Smith, Samuel M.,Walden, Daniel M.,Taylor, James E.,Brice, Zamira,Robinson, Emily R. T.,Fallan, Charlene,Cordes, David B.,Slawin, Alexandra M. Z.,Richardson, H. Camille,Grove, Markas A.,Cheong, Paul Ha-Yeon,Smith, Andrew D.
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supporting information
p. 3200 - 3206
(2018/02/22)
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- Tumor-associated carbonic anhydrase isoform IX and XII inhibitory properties of certain isatin-bearing sulfonamides endowed with in vitro antitumor activity towards colon cancer
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Three series of indolinone-based sulfonamides (3a–f, 6a–f and 9a–f) were in vitro evaluated as inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII, using a stopped-flow CO2 hydrase assay. All the investigated sulfonamides displayed single- or double-digit nanomolar inhibitory activities towards both hCA IX (KIs: 6.2–64.8 nM) and XII (KIs: 7.1–55.6 nM) isoforms. All sulfonamides (3a–f, 6a–f and 9a–f) were in vitro examined for their potential anticancer activity against colorectal cancer HCT-116 and breast cancer MCF-7 cell lines. Sulfonamide 9e was found to be the most potent counterpart against HCT-116 (IC50 = 3.67 ± 0.33 μM). Sulfonamide 9e displayed good selectivity profile for inhibition of the tumor-associated isoforms (CAs IX & XII) over the off-target cytosolic CAs I and II. 9e was screened for cell cycle disturbance and apoptosis induction in HCT-116 cells. It was found to persuade cell cycle arrest at G2-M stage as well as alter the Sub-G1 phase. Also, 9e induced the intrinsic apoptotic mitochondrial pathway in HCT-116 cells via down-regulation of the anti-apoptotic protein Bcl-2 level with concurrent boosting the pro-apoptotic Bax, caspase-9, caspase-3, cytochrome C and p53 levels.
- Eldehna, Wagdy M.,Nocentini, Alessio,Al-Rashood, Sara T.,Hassan, Ghada S.,Alkahtani, Hamad M.,Almehizia, Abdulrahman A.,Reda, Ahmed M.,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
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p. 425 - 432
(2018/09/21)
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- Design and Synthesis of DNA-Interactive β-Carboline–Oxindole Hybrids as Cytotoxic and Apoptosis-Inducing Agents
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A new series of (E)-3-[(1-aryl-9H-pyrido[3,4-b]indol-3-yl)methylene]indolin-2-one hybrids were synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines, namely, HCT-15, HCT-116, A549, NCI-H460, and MCF-7, including HFL. Among the tested compounds, (E)-1-benzyl-5-bromo-3-{[1-(2,5-dimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl]methylene}indolin-2-one (10 s) showed potent cytotoxicity against HCT-15 cancer cells with an IC50 value of 1.43±0.26 μm and a GI50 value of 0.89±0.06 μm. Notably, induction of apoptosis by 10 s on the HCT-15 cell line was characterized by using different staining techniques, such as acridine orange/ethidium bromide (AO/EB) and DAPI. Further, to understand the mechanism of anticancer effects, various assays such as annexin V-FITC/PI, DCFDA, and JC-1were performed. The flow cytometric analysis revealed that compound 10 s arrests the HCT-15 cancer cells at the G0/G1 phase of the cell cycle. Additionally, western blot analysis indicated that treatment of 10 s on HCT-15 cancer cells led to decreased expression of anti-apoptotic Bcl-2 and increased protein expression of both pro-apoptotic Bax and caspase-3, -8, and -9, and cleaved PARP with reference to actin. Next, a clonogenic assay revealed the inhibition of colony formation in HCT-15 cancer cells by 10 s in a dose-dependent manner. Moreover, upon testing on normal human lung cells (HFL), the compounds were observed to be safer with a low toxicity profile. In addition, viscosity and molecular-docking studies showed that compound 10 s has typical intercalation with DNA.
- Tokala, Ramya,Thatikonda, Sowjanya,Vanteddu, Usha Sree,Sana, Sravani,Godugu, Chandraiah,Shankaraiah, Nagula
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p. 1909 - 1922
(2018/09/14)
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- Development of Novel Chloramphenicol Scaffold-Based Chiral Hydroxyl Oxazoline Ligands and Their Application to the Asymmetric Alkynylation of Isatins
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The synthesis of new chloramphenicol base-derived chiral hydroxyl oxazoline ligands, and their use in the first Zn(OTf)2-catalyzed enantioselective alkynylation of isatins are described. This transformation features mild reaction conditions, a remarkably broad substrate scope, and excellent functional group tolerance, affording the corresponding tertiary propargylic alcohols in high yields and with high enantioselectivities. The application of chiral hydroxyl oxazolines as ligands in Zn(II)-catalyzed asymmetric alkynylation reactions is unprecedented. (Figure presented.).
- Chen, Lei,Huang, Guanxin,Liu, Minjie,Huang, Zedu,Chen, Fen-Er
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supporting information
p. 3497 - 3501
(2018/09/14)
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- Nickel(II)-Catalyzed Asymmetric Propargyl [2,3] Wittig Rearrangement of Oxindole Derivatives: A Chiral Amplification Effect
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A highly enantioselective [2,3] Wittig rearrangement of oxindole derivatives was realized by using a chiral N,N′-dioxide/NiII complex as the catalyst under mild reaction conditions. A strong chiral amplification effect was observed, and allowed access to chiral 3-hydroxy 3-substituted oxindoles bearing allenyl groups in high yields and enantioselectivities (up to 92 % ee) by using a ligand with only 15 % ee. A reasonable explanation was given based on the experimental investigations and X-ray crystal structures of enantiomerically pure and racemic catalysts. Moreover, the first catalytic kinetic resolution of racemic oxindole derivatives by a [2,3] Wittig rearrangement was realized with high efficiency and stereoselectivity.
- Xu, Xi,Zhang, Jianlin,Dong, Shunxi,Lin, Lili,Lin, Xiaobin,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 8734 - 8738
(2018/07/14)
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- Organocatalytic Asymmetric Synthesis of Bridged Acetals with Spirooxindole Skeleton
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The first highly diastereo- and enantioselective synthesis of bridged O,O-acetals embedded with spirooxindoles has been developed. Dioxindoles and 2-hydroxy cinnamaldehydes were employed as the reaction partners in this method. The desired products were obtained via diaryl prolinol TBS ether catalyzed Michael reaction followed by acetal formation with TFA.
- Balha, Megha,Pan, Subhas Chandra
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p. 14703 - 14712
(2018/11/23)
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- Electrocatalytic C-H/N-H Coupling of 2′-Aminoacetophenones for the Synthesis of Isatins
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2′-Aminoacetophenones undergo a C(sp3)-H oxidation followed by intramolecular C-N bond formation by virtue of a simple electrochemical oxidation in the presence of n-Bu4NI, providing various isatins with moderate to good yields. The reaction intermediates were detected, and a radical-based pathway was proposed.
- Qian, Peng,Su, Ji-Hu,Wang, Yukang,Bi, Meixiang,Zha, Zhenggen,Wang, Zhiyong
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p. 6434 - 6440
(2017/06/23)
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- Direct N-H/α,α,β,β-C(sp3)-H functionalization of piperidine via an azomethine ylide route: synthesis of spirooxindoles bearing 3-substituted oxindoles
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A protocol for the direct functionalization of N-H/α,α,β,β-C(sp3)-H of piperidine without any metal or external oxidants is reported. This reaction is promoted by 4-(trifluoromethyl)benzoic acid via an azomethine ylide intermediate. This is a simple method for the synthesis of spirooxindoles bearing 3-substituted oxindole moieties.
- Du, Yanlong,Yu, Aimin,Jia, Jiru,Zhang, Youquan,Meng, Xiangtai
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supporting information
p. 1684 - 1687
(2017/02/10)
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- Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in?vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies
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Herein we present the design, synthesis, and biological evaluation of three different series of novel sulfonamides (3a-f, 6a-f and 9a-f) incorporating substituted indolin-2-one moieties (as tails) linked to benzenesulfonamide (as zinc anchoring moieties) through aminoethyl or (4-oxothiazolidin-2-ylidene)aminoethyl linkers. The synthesized sulfonamides were evaluated in?vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IV and VII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with KIs in the range of 42–8550.9?nM, hCA II in the range of 5.9–761?nM; hCA IV in the range of 4.0–2069.5?nM, whereas hCA VII in the range of 13.2–694?nM. Molecular docking studies were carried out for some of the tested compounds within the hCA II active site, allowed us to rationalize the obtained inhibition results.
- Eldehna, Wagdy M.,Al-Ansary, Ghada H.,Bua, Silvia,Nocentini, Alessio,Gratteri, Paola,Altoukhy, Ayman,Ghabbour, Hazem,Ahmed, Hanaa Y.,Supuran, Claudiu T.
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p. 521 - 530
(2017/01/24)
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- Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino) benzenesulfonamides: Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular modelling studies
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Herein we report the synthesis of two series of novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino)benzenesulfonamides (4a-m and 7a-g). All the newly prepared sulfonamides were in vitro investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IV and IX, using a stopped-flow CO2 hydrase assay. In particular, hCA isoforms II and IX (tumor-associated) were more susceptible to inhibition by the synthesized derivatives, with KIs in the range of 2.6–598.2 nM for hCA II, and of 16.1–321 nM for hCA IX. All compounds (4a-m and 7a-g) were evaluated for their anti-proliferative activity against breast cancer MCF-7 and colorectal cancer Caco-2 cell lines. Compound 4c was found to be the most potent derivative against MCF-7 (IC50 = 3.96 ± 0.21 μM), while 4j was the most active member against Caco-2 cells (IC50 = 5.87 ± 0.37 μM). Compound 4c induced the intrinsic apoptotic mitochondrial pathway in MCF-7 cells; evidenced by the enhanced expression of the pro-apoptotic protein Bax and the reduced expression of the anti-apoptotic protein Bcl-2, and the up-regulated active caspase-9 and caspase-3 levels.
- Eldehna, Wagdy M.,Abo-Ashour, Mahmoud F.,Nocentini, Alessio,Gratteri, Paola,Eissa, Ibrahim H.,Fares, Mohamed,Ismael, Omnia E.,Ghabbour, Hazem A.,Elaasser, Mahmoud M.,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
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p. 250 - 262
(2017/08/14)
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- Synthesis and bio-evaluation of quaternary centered 3-hydroxy-3-(trifluoromethyl)indolin-2-one derivatives for anticancer and antimicrobial activities
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Abstract: A series of C(3)-trifluoromethylated compounds derived from N-substituted isatins were synthesized. The biological activity of all 3-hydroxy-3-(trifluoromethyl)indolin-2-one derivatives have been evaluated for in vitro cytotoxic activity and antibacterial activity. The active compounds were screened against nuclear xenobiotic receptor CAR (PDB ID: 1XLS), PIM1 kinase (PDB ID: 2O65), and CDK2 kinase (PDB ID: 3QHR) by using in silico molecular docking studies to obtain lead molecules. In addition to its potential anticancer activity, 5-bromo-3-ethynyl-3-hydroxy-1-(prop-2-yn-1-yl)indolin-2-one also showed specific antibacterial activity against S. aureus. Graphical abstract: [Figure not available: see fulltext.]
- Bikshapathi, Raktani,Prathima, Parvathaneni Sai,Yashwanth,Pamanji,Jagadeeshkumar,Maheshwari,Rao, J. Venkateswara,Murty,Rao, V. Jayathirtha
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p. 757 - 764
(2017/03/17)
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- A Highly Stereoselective Chiral Auxiliary-assisted Reductive Cyclization to Furoindoline
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Highly stereoselective furoindoline derivatives were synthesized by exploring the imidazolidinone-based chiral auxiliary-mediated aldol adduct. The one-pot reductive cyclization was achieved through NiCl2.6H2O/NaBH4.
- Kumar, Kapil,More, Shital S.,Khatik, Gopal L.,Rawal, Ravindra K.,Nair, Vipin A.
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p. 2696 - 2702
(2017/09/26)
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- A facile one pot C[sbnd]C and C[sbnd]N bond formation for the synthesis of spiro-benzodiazepines and their cytotoxicity
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An efficient, multicomponent and environmentally benign protocol has been developed for the synthesis of spiro-benzodiazepines through C[sbnd]C and C[sbnd]N bond formations in a single step. This one-pot protocol proceeds via three component reaction of o
- Nagaraju, Burri,Kovvuri, Jeshma,Babu, K. Suresh,Adiyala, Praveen Reddy,Nayak, V. Lakshma,Alarifi, Abdullah,Kamal, Ahmed
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p. 6969 - 6976
(2017/11/13)
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- Diversity-Oriented Synthesis of Oxacyclic Spirooxindole Derivatives through Ring-Closing Enyne Metathesis and Intramolecular Pauson–Khand (2+2+1) Cyclization of Oxindole Enynes
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An efficient approach for a reagent-based diversity-oriented synthesis (DOS) of novel fused spirooxindole scaffolds from oxindole enynes has been developed. The reaction involves a metal-catalyzed C-3 allylation/vinylation/homoallylation of N-substituted isatins which gives rise to the corresponding alcohols that can be converted into the required enynes. Further transformation to diverse complex molecular scaffolds proceeds via a subsequent ruthenium-catalyzed ring-closing enyne metathesis (RCEYM), or cobalt-catalyzed intramolecular Pauson–Khand (2+2+1) cyclization reaction (IPKR). This strategy provides a facile approach to various spirooxindole-vinyldihydropyrans/tetrahydrooxepines and spirocyclic fused cyclopentenones in good to excellent yields. (Figure presented.).
- Kandimalla, Satheeshkumar Reddy,Sabitha, Gowravaram
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supporting information
p. 3444 - 3453
(2017/09/25)
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- Synthesis, spectroscopic characterization and antimicrobial potential of certain new isatin-indole molecular hybrids
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Molecular hybridization has a wide application in medicinal chemistry to obtain new biologically active compounds. New isatin-indole molecular hybrids 5a-n have been synthesized and characterized by various spectroscopic tools. The in vitro antimicrobial potential of the prepared compounds 5a-n was assessed using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against a panel of Gram-negative bacteria, Gram-positive bacteria and fungi. Most of the synthesized compounds 5a-n showed weak activities against Gram-negative bacteria while compounds 5b and 5c exhibited good activities against Gram-positive bacteria. On the other hand, compound 5j emerged as the most active compound towards Candida albicans (C. albicans), with an MIC value of 3.9 μg/mL, and compound 5g as the most active congener towards Asperagillus Niger (A. Niger), with an MIC value of 15.6 μg/mL. Moreover, compound 5h manifested the best anti-P. notatum effect, with an MIC value of 7.8 μg/mL, making it equipotent with compound 5g.
- Al-Wabli, Reem I.,Zakaria, Azza S.,Attia, Mohamed I.
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- Iodine-Catalyzed Oxidation of N-Substituted Indoles by using Chloramine-B: A Facile and Practical Approach to Isatins
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An efficient method for the iodine-catalyzed oxidation of N-substituted indoles by using chloramine-B under mild reaction conditions was explored. This reaction was found to be tolerant to a variety of functional groups and provided the corresponding isatins in moderate to excellent yields. In addition, application of this method to the one-pot synthesis of 3-hydroxyoxindole and N-methylisatin oxime was realized.
- Liu, Peijun,Guo, Jiajing,Wei, Wentao,Liu, Xiaozu,Sun, Pinghua
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supporting information
p. 2105 - 2109
(2016/05/09)
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- A Palladium-Catalyzed Double Carbonylation Approach to Isatins from 2-Iodoanilines
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A high-yielding procedure for the synthesis of isatins has been developed. Sequential Pd-catalyzed double carbonylation of 2-iodoanilines with near stoichiometric amounts of CO followed by acid-promoted cyclization readily affords an array of isatins. The conversion of 2-iodoanilines to isatins in good to excellent yields was found to proceed with good functional group tolerance. This protocol proved adaptable to 13C-isotope labeling of isatins, which was extended to the synthesis of the 13C-isotope labeled antiviral drug metisazone and the experimental anti-schizophrenia drug ML137.
- Laursen, Simon R.,Jensen, Mikkel T.,Lindhardt, Anders T.,Jacobsen, Mikkel F.,Skrydstrup, Troels
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supporting information
p. 1881 - 1885
(2016/05/09)
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- Discovery of pyrrolospirooxindole derivatives as novel cyclin dependent kinase 4 (CDK4) inhibitors by catalyst-free, green approach
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Aiming to develop a new target for the anticancer treatment, a series of 5′H-spiro[indoline-3,4′-pyrrolo [1,2-A]quinoxalin]-2-ones has been synthesized by simple, highly efficient and environmentally friendly method in excellent yields under catalyst-free
- Kamal, Ahmed,Mahesh, Rasala,Nayak, V. Lakshma,Babu, Korrapati Suresh,Kumar, G. Bharath,Shaik, Anver Basha,Kapure, Jeevak Sopanrao,Alarifi, Abdullah
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p. 476 - 485
(2015/12/30)
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- Water-Promoted Regiospecific Azidolysis and Copper-Catalyzed Azide-Alkyne Cycloaddition: One-Pot Synthesis of 3-Hydroxy-1-alkyl-3-[(4-aryl/alkyl-1H-1,2,3-triazol-1-yl)methyl]indolin-2-ones
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An efficient, eco-friendly, base free, one-pot, sequential protocol was developed for epoxide azidolysis and copper-catalyzed azide-alkyne cycloaddition using water as the solvent for the synthesis of 3-hydroxy-1-alkyl-3-[(4-aryl/alkyl-1H-1,2,3-triazol-1-yl)methyl]indolin-2-ones. The optimized reaction conditions have been generalized in the case of aromatic as well as aliphatic alkyne partners to afford good yields and high regioselectivity.
- Kumar, Kapil,Konar, Debabrata,Goyal, Sandeep,Gangar, Mukesh,Chouhan, Mangilal,Rawal, Ravindra K.,Nair, Vipin A.
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p. 9757 - 9764
(2016/10/31)
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- Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies
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A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 6i, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-4.36 μM, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted in A549 cells.
- Senwar, Kishna Ram,Sharma, Pankaj,Reddy, T. Srinivasa,Jeengar, Manish Kumar,Nayak, V. Lakshma,Naidu,Kamal, Ahmed,Shankaraiah, Nagula
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p. 413 - 424
(2015/09/01)
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- Iodine-Mediated C-H Functionalization of sp, sp2, and sp3 Carbon: A Unified Multisubstrate Domino Approach for Isatin Synthesis
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(Chemical Equation Presented) Molecular iodine-promoted efficient construction of isatins from 2′-aminophenylacetylenes, 2′-aminostyrenes, and 2′-amino-β-ketoesters is developed via oxidative amidation of sp, sp2, and sp3 C-H bonds. The reaction involves consecutive iodination, Kornblum oxidation, and intramolecular amidation in a single reactor. The present method meets all of the atom and redox economy principles.
- Satish, Gandhesiri,Polu, Ashok,Ramar, Thangeswaran,Ilangovan, Andivelu
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p. 5167 - 5175
(2015/05/27)
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- Catalyst-free, one pot and three-component synthesis of 4′-phenyl-1′H-spiro[indoline-3,2′-quinazolin]-2-ones and 2,4-diphenyl-1,2-dihydroquinazolines
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A simple, green, efficient and three-component procedure has been developed for the synthesis of 4′-phenyl-1′H-spiro[indoline-3,2′-quinazolin]-2-ones (4a-m and 6a-g) and 2,4-diphenyl-1,2-dihydroquinazolines (8a-l) by the reaction of 2-aminobenzophenones,
- Kamal, Ahmed,Babu, Korrapati Suresh,Chandrasekhar, Cheemalamarri,Nagaraju, Burri,Visweswara Sastry,Ganesh Kumar
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supporting information
p. 6373 - 6376
(2015/11/16)
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- Microwave synthesis, characterization, and antimicrobial activity of some novel isatin derivatives
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Three series of isatin derivatives [3-hydrazino, 3-thiosemicarbazino, and 3-imino carboxylic acid derivatives] were synthesized employing microwave irradiation. The prepared compounds were characterized by FT-IR, NMR, elemental analysis, and X-ray crystal
- El-Faham, Ayman,Hozzein, Wael N.,Wadaan, Mohammad A. M.,Khattab, Sherine N.,Ghabbour, Hazem A.,Fun, Hoong-Kun,Siddiqui, Mohammed Rafiq
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- New organocatalytic asymmetric synthesis of highly substituted chiral 2-oxospiro-[indole-3,4'- (1',4'-dihydropyridine)] derivatives
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Herein, we report our preliminary results concerning the first promising asymmetric synthesis of highly functionalized 2-oxospiro-[indole-3,4'-(1',4'-dihydropyridine)] via the reaction of an enamine with isatylidene malononitrile derivatives in the presen
- Auria-Luna, Fernando,Marqués-López, Eugenia,Mohammadi, Somayeh,Heiran, Roghayeh,Herrera, Raquel P.
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p. 15807 - 15826
(2015/12/01)
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- Oxidative dimerization of 2-oxindoles promoted by KOtBu-I2: Total synthesis of (±)-folicanthine
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A transition-metal-free oxidative coupling of 2-oxindoles has been demonstrated in the presence of 1.2 equiv each of potassium tert-butoxide and iodine. The method yields a diverse range of structurally different homo- and heterodimerized 2-oxindoles bearing vicinal all-carbon quaternary centers of great synthetic importance. A radical-driven pathway has been tentatively proposed.
- Ghosh, Santanu,Chaudhuri, Saikat,Bisai, Alakesh
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supporting information
p. 1373 - 1376
(2015/03/30)
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- An efficient route to synthesize isatins by metal-free, iodine-catalyzed sequential C(sp3)-H oxidation and intramolecular C-N bond formation of 2′-aminoacetophenones
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A novel molecular I2-catalyzed synthesis of isatins through C(sp3)-H oxidation and intramolecular C-N bond formation of 2′-aminoacetophenones with excellent yields up to 97% under transition metal, base, additive, peroxide and ligand free conditions is described. The present protocol is suitable for gram scale synthesis of isatins and retained its high yield. Further, the synthetic utility of this present reaction towards synthesis of bioactive 3-hydroxy-2-oxindoles and oxindoles is demonstrated. This journal is
- Rajeshkumar, Venkatachalam,Chandrasekar, Selvaraj,Sekar, Govindasamy
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p. 8512 - 8518
(2014/12/10)
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- Direct amidation of 2'-aminoacetophenones using I2-TBHP: A unimolecular domino approach toward isatin and iodoisatin
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Synthesis of isatin and iodoisatin from 2'-aminoacetophenone was achieved via oxidative amido cyclization of the sp3 C-H bond using I 2-TBHP as the catalytic system. The reaction proceeds through sequential iodination, Kornblum oxidation, and amidation in one pot. This method is simple, atom economic, and works under metal- and base-free conditions.
- Ilangovan, Andivelu,Satish, Gandhesiri
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p. 4984 - 4991
(2014/06/23)
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- Copper-mediated selective C-H activation and cross-dehydrogenative C-N coupling of 2′-aminoacetophenones
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Isatins were obtained by cross-dehydrogenative C-N annulation and dealkylative C-N annulation of 2′-N-aryl/alkylaminoacetophenones and 2′-N,N-dialkylaminoacetophenones respectively in the presence of Cu(OAc)2·H2O/NaOAc/air. However, on reaction with CuBr, 2′-N-benzylaminoacetophenones underwent selective oxidation of an α-methylene group of amine rather than the 2-acetyl group to provide corresponding benzamides exclusively. Base played an important role in selective oxidation by lowering the temperature and time.
- Ilangovan, Andivelu,Satish, Gandhesiri
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supporting information
p. 5726 - 5729
(2013/12/04)
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- Efficient green synthesis of isoindigo derivatives using sulfonic-acid-functionalized nanoporous silica (SBA-Pr-SO3H) catalyst and study of their antimicrobial properties
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An efficient green condensation reaction has been developed for synthesis of trans-isoindigo derivatives using SBA-Pr-SO3H with pore size of 6 nm as a heterogeneous nanoporous acid catalyst under solvent-free conditions. Isoindigo derivatives have many industrial applications, e.g., dyes, drugs, organic solar cells, and semiconductor memories. The antimicrobial activities of these compounds have also been tested.
- Gholamzadeh, Parisa,Mohammadi Ziarani, Ghodsi,Badiei, Alireza,Abolhassani Soorki, Ali,Lashgari, Negar
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p. 3925 - 3936
(2013/11/19)
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