- Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors
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Histone deacetylases (HDACs) are zinc-dependent or NAD+ dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds synthesized have exhibited moderate Hela cell nuclear extract inhibitory activities, among which compound 25a (IC50 = 10.13 nM) has shown the best efficacy. The anti-proliferative activities of some of these compounds were also discussed.
- Jin, Kang,Li, Shanshan,Li, Xiaoguang,Zhang, Jian,Xu, Wenfang,Li, Xuechen
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p. 4728 - 4736
(2015/08/03)
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- Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as SARS-CoV 3C-like protease inhibitors
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The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains a chymotrypsin-like main protease analogous to that of the main picornavirus protease, 3CLpro. 3CLpro plays a pivotal role in the viral replication cycle and is a potential target for SARS inhibitor development. A series of isatin derivatives as possible SARS-CoV 3CL pro inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CLpro. Structure-activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k1 showed most potent inhibitory activity against 3CLpro (IC50 = 1.04 μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.
- Liu, Wei,Zhu, He-Min,Niu, Guo-Jun,Shi, En-Zhi,Chen, Jie,Sun, Bo,Chen, Wei-Qiang,Zhou, Hong-Gang,Yang, Cheng
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p. 292 - 302
(2014/01/17)
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- A novel strategy to the synthesis of 4-anilinoquinazoline derivatives
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A novel approach to prepare 4-anilinoquinazoline derivatives based on the transformation of indoline-2,3-dione to formamidine was developed. The processes with this approach are simple, efficient, and environmentally friendly. The efficiency of this approach was evaluated by synthesizing 17 4-anilinoquinazolines and comparing the obtained yields with those achievable through conventional synthetic methods. It was the first time that compounds 8d, 8e, 8h, and 13b-f were synthesized. The characteristics of the IR and the UV spectra of these compounds and the effects of their substituents on the spectra were observed.
- Wang, Zheng,Wang, Cuiling,Sun, Yanni,Zhang, Ning,Liu, Zhulan,Liu, Jianli
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p. 906 - 913
(2014/01/23)
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- Structure-based design, synthesis, andanticonvulsant activity of isatin-1-N-phenylacetamide derivatives
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In an effort to develop the potent anticonvulsant agents, a series of novel isatin-1-N-phenylacetamide derivatives was synthesized and screened for their in vivo anticonvulsant activity against maximal electroshock test and evaluated for their neurotoxicity by the rotarod test at the same dose levels. Ten compounds exhibited the anticonvulsant activity. 2-(5-Methyl-2,3-dioxoindolin-1- yl)-N-phenylacetamide (4b) was found to be the most potent compound of the series with an ED50 of 91.3 mg/kg, TD50 of >1,000 mg/kg, a higher protective index (PI = TD50/ED50, >11) was gained than the reference drug phenobarbital and carbamazepine. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore. Springer Science+Business Media 2013.
- Xie, Chao,Tang, Li-Ming,Li, Fu-Nan,Guan, Li-Ping,Pan, Cheng-Yan,Wang, Si-Hong
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p. 2161 - 2168
(2014/05/06)
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- Synthesis of novel triazol compounds containing isatin as potential antibacterial and antifungal agents by microwave and conventional methods
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Microwave irradiation has been used to accelerate the conversion of isatin (1a) and 5-nitroisatin (1b) into their Schiff bases 3-[5′-aryl(alkyl)- 2′,4′-dihydro-1′,2′,4′-triazol-3′-on- 4′-yl]iminoisatin (3a-g) and 3-[5′-aryl(alkyl)-2′,4′- dihydro-1′,2′,4′-triazol-3′-on-4′-yl] imino-5-nitroisatin (4a-g), respectively. Reaction was achieved by microwave-induced technique, which reduced the reaction time drastically and improved the yield when compared to conventional heating. The newly synthesised bases showed moderate antimicrobial activity against the standard bacterial and fungal organisms tested.
- Oezil, Musa,Mentese, Emre,Yilmaz, Fatih,Islamoglu, Fatih,Kahveci, Bahittin
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scheme or table
p. 268 - 271
(2011/10/05)
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- An improved synthesis of isonitrosoacetanilides
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A novel two-step synthesis of isonitrosoacetanilides [2-(hydroxyimino)-N- phenylacetamides] has been developed, involving the initial acylation of aniline derivatives with 2,2-diacetoxyacetyl chloride, followed by reaction with hydroxylamine hydrochloride. The method works equally well with a variety of different aniline derivatives, including those with poor aqueous solubility and those containing electron rich ortho-substituents, neither of which react well under traditional conditions.
- Rewcastle, Gordon W.,Sutherland, Hamish S.,Weir, Claudette A.,Blackburn, Adrian G.,Denny, William A.
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p. 8719 - 8721
(2007/10/03)
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- Study of some biorelevant complexes of manganese(II) with active imines
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Some new manganese(II) complexes of biologically relevant ligands, hydrazinecarboxamide and hydrazinecarbothioamide of 5-nitro-indol-2,3-dione and 6-nitro-indol-2,3-dione of the composition [MnCl(N∩X)H 2O] and [Mn(N∩X)2] have been isolated, where N ∩X = donor system of the ligand and X is oxygen or sulphur. The complexes have been characterized by the elemental analysis, molar conductance, magnetic measurements, molecular weight determinations, IR and ESR spectral studies. On the basis of spectroscopic studies, it has been inferred that the manganese(II) complexes are consistent with the tetrahedral geometry. The magnetic measurements reveal that the manganese(II) complexes are high spin in nature. All the ligands and their corresponding complexes have been screened for their antifungal and antibacterial activities.
- Garg, Rekha,Saini, Mahesh Kumar,Fahmi, Nighat,Singh
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p. 2433 - 2438
(2007/10/03)
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- Microwave assisted preparation of isatins and synthesis of (±)- convolutamydine-A
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Microwave assisted preparation of a number of isatin derivatives is reported. A simple synthesis of (±)-convolutamydine-A, a potent compound against leukemia cells, is presented.
- Jnaneshwara,Bedekar,Deshpande
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p. 3627 - 3633
(2007/10/03)
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- Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors
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A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'- halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'- chloro-3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure- activity relationships in this series are also discussed.
- Yamagishi,Yamada,Ozaki,Asao,Shimizu,Suzuki,Matsumoto,Matsuoka,Matsumoto
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p. 2085 - 2094
(2007/10/02)
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