- Sio2 mediated reaction of isatin with N-halosaccharins: A regiospecific preparation of 5-haloisatins
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N-halosaccharins (5 mmol) react smoothly at room temperature with isatin (5 mmol) in the presence of SiO2 (5 g) to produce specifically the 5-halo derivative. Using this procedure, 5-chloroisatin was obtained in 48% purified yield (72 h), 5-bromoisatin in 58% (12 h) and 5-iodoisatin in 80% (8 h).
- De Souza, Soraia P.L.,Da Silva, Joaquim Fernando M.,De Mattos, Marcio C.S.
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Read Online
- A Facile Synthesis of Novel Isatinspirooxazine Derivatives and Potential in vitro Anti-Proliferative Activity
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Novel isatinspirooxazine derivatives were designed and synthesized as potential anti-proliferative agents. The new compounds were obtained from aldol condensation reactions between isatin and 3-(hydroxyimino)butan-2-one in the presence of an organic base in order to generate an aldol adduct, followed by cyclization in trifluoroacetic acid, providing the desired isatinspirooxazines in 30 to 80percent yield. All the synthesized compounds, including the starting material and the synthetic intermediates, were tested for in vitro anti-proliferative activity against cell lines MCF-7 and MDA-MB231 (breast cancer) and A549 (lung cancer), highlighting the compound 4-methyl,5'-methyl-spiro[(5-aza-4-eno-3-one-cyclohexane)-1,3'-(1H-indol-one)] with an IC50 (half maximal inhibitory concentration) = 0.34 μM, more potent than the reference drug, doxorubicin (IC50 = 1.88 μM), in breast cancer line MDA-MB231.
- Santos, Iara S.,Guerra, Fabiana S.,Bernardino, Lucas F.,Fernandes, Patrícia D.,Hamerski, Lidilhone,Silva, Bárbara V.
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Read Online
- R4NHal/NOHSO4: A Usable System for Halogenation of Isoxazoles, Pyrazoles, and beyond
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A new convenient and versatile halogenating system (R4NHal/NOHSO4), giving straightforward and general access to halogenated 3,5-diaryl- and alkylarylisoxazoles, pyrazoles and electron-rich benzenes from the corresponding scaffolds, is suggested. The method provides excellent regioselectivity, scalability to the gram scale, and a broad scope for both aromatics and halogens. A three-step, one-pot reaction protocol was developed, and a series of 3,5-diaryl-4-haloisoxazoles has been efficiently synthesized from 1,2-diarylcyclopropanes under suggested nitrosating-halogenating conditions.
- Bondarenko, Oksana B.,Karetnikov, Georgy L.,Komarov, Arseniy I.,Pavlov, Aleksandr I.,Nikolaeva, Svetlana N.
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supporting information
p. 322 - 332
(2021/01/14)
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- Study on synthesis of some substituted N-propargyl isatins by propargylation reaction of corresponding isatins using potassium carbonate as base under ultrasound- and microwave-assisted conditions
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Substituted N-propargyl isatins were synthesized by SN2 reaction of corresponding substituted isatins with propargyl bromide in the presence of anhydrous K2CO3 as base. We reported about study on systematically synthesis of these compounds using heating procedures under different reaction conditions, including microwave-assisted heating conditions at power of 100?W (Procedure A), conventional heating conditions in water bath at 50?°C in acetonitrile (Procedure B), and conventional heating conditions in water bath at 50?°C in DMF (procedure C). The best procedure A was deduced based on the investigations on the reaction conditions. Almost all substituted N-propargyl isatins were new, except compounds with R of H, 5-Me, 5-Cl and 5-Br substituents. The structures of the obtained compounds were confirmed by the modern spectroscopic methods.
- Tri, Nguyen Minh,Thanh, Nguyen Dinh,Ha, Luong Ngoc,Anh, Dang Thi Tuyet,Toan, Vu Ngoc,Giang, Nguyen Thi Kim
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p. 4793 - 4801
(2021/05/31)
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- Synthesis and evaluation of tryptanthrins as antitumor agents
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Here, an efficient and convenient method has been developed for the rapid preparation of N-substituted tryptanthrin analogues through the reaction of tryptanthrins and secondary amines under mild reaction conditions. All compounds were tested for their anti-tumor activity in cancer cell lines by MTT assay. The results showed that some of them exhibited anti-tumor activity against human tumor cell lines A549, HCT116, MDA-MB-231 with IC50 mean values at a low micromolar level. In particular, compound 3b induced G2/S cell cycle arrest and apoptosis in A549 cells dose-dependently.
- Hou, Baolong,Li, Wenyu,Liu, Jianli,Wang, Cuiling,Zhou, Ying
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supporting information
(2021/10/01)
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- 1-benzylisatin derivative as well as synthesis method and application thereof
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The invention relates to a 1-benzylisatin derivative as well as a synthesis method and application thereof, belongs to the technical field of medicines, and relates to a general formula (I) in which R1, R2 and R3 are different substituents. The invention discloses structures of the compounds, a synthesis method of the compounds, inhibitory activity of acetylcholin esterase and inhibitory activityof histone deacetylase 6; and the compounds can be further developed into drugs for treating Alzheimer's disease.
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Paragraph 0082-0086
(2020/10/20)
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- A rhodium(ii) catalysed domino synthesis of azepino fused diindoles from isatin tethered: N -sulfonyl-1,2,3-triazoles and indoles
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An efficient and convenient protocol for the synthesis of a novel class of azepino fused diindoles from isatin tethered N-sulfonyl-1,2,3-triazoles and indoles has been disclosed. The reaction proceeds via denitrogenative aza-vinyl rhodium carbene formation to give a carbonyl ylide, which with indole results in 1,3-dipolar cycloaddition followed by sequential semipinacol rearrangement/ring expansion/oxidation to produce azepino fused diindoles. The reaction shows a broad substrate scope giving up to 81% yield. Furthermore, reversible catalytic hydrogenation and photophysical studies were carried out to demonstrate the application of these molecules.
- Kahar, Nilesh,Jadhav, Pankaj,Reddy, R. V. Ramana,Dawande, Sudam
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supporting information
p. 1207 - 1210
(2020/02/04)
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- Further Studies on Triazinoindoles as Potential Novel Multitarget-Directed Anti-Alzheimer's Agents
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The inadequate clinical efficacy of the present anti-Alzheimer's disease (AD) drugs and their low impact on the progression of Alzheimer's disease in patients have revised the research focus from single targets to multitarget-directed ligands. A novel series of substituted triazinoindole derivatives were obtained by introducing various substituents on the indole ring for the development of multitarget-directed ligands as anti-AD agents. The experimental data indicated that some of these compounds exhibited significant anti-AD properties. Among them, 8-(piperidin-1-yl)-N-(6-(pyrrolidin-1-yl)hexyl)-5H-[1,2,4]triazino[5,6-b]indol-3-amine (60), the most potent cholinesterase inhibitor (AChE, IC50 value of 0.32 μM; BuChE, IC50 value of 0.21 μM), was also found to possess significant self-mediated Aβ1-42 aggregation inhibitory activity (54% at 25 μM concentration). Additionally, compound 60 showed strong antioxidant activity. In the PAMPA assay, compound 60 exhibited blood-brain barrier penetrating ability. An acute toxicity study in rats demonstrated no sign of toxicity at doses up to 2000 mg/kg. Furthermore, compound 60 significantly restored the cognitive deficits in the scopolamine-induced mice model and Aβ1-42-induced rat model. In the in silico ADMET prediction studies, the compound satisfied all the parameters of CNS acting drugs. These results highlighted the potential of compound 60 to be a promising multitarget-directed ligand for the development of potential anti-AD drugs.
- Patel, Dushyant V.,Patel, Nirav R.,Kanhed, Ashish M.,Teli, Divya M.,Patel, Kishan B.,Gandhi, Pallav M.,Patel, Sagar P.,Chaudhary, Bharat N.,Shah, Dharti B.,Prajapati, Navnit K.,Patel, Kirti V.,Yadav, Mange Ram
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p. 3557 - 3574
(2020/11/18)
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- Visible-Light-Mediated Dearomatisation of Indoles and Pyrroles to Pharmaceuticals and Pesticides
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Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N-protected and protection-free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.
- Schilling, Waldemar,Zhang, Yu,Riemer, Daniel,Das, Shoubhik
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supporting information
p. 390 - 395
(2019/12/15)
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- Synthesis and Ameliorative Effect of Isatin–Mesalamine Conjugates on Acetic Acid-induced Colitis in Rats
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A series of new isatin–mesalamine conjugates (9a–g) were synthesized via conjugation of isatin (3a) and its derivatives (3b–3d, 4, 5, and 6) with mesalamine (7) by using chloroacetyl chloride as a bifunctional linker. Compounds 3a–3d were prepared by employing Sandmeyer reaction. Compounds 4, 5, and 6 were obtained from isatin (3a) via previously reported methods. The synthesized compounds were characterized by IR, mass, 1H NMR, and 13C NMR spectral techniques. Synthesized compounds (3a–d, 4, 5, 6, and 9a–g) were evaluated for in vitro antioxidant activity by DPPH assay method using ascorbic acid as standard. Hybrids 9b (IC50?=?368.6?±?3.5?μM) and 9f (IC50?=?335.1?±?2.9?μM) showed better antioxidant activity than its parent compounds such as 3a (IC50?=?556.8?±?2.9?μM), 5 (IC50?=?511.9?±?3.6?μM), and 7 (IC50?=?768.9?±?2.7?μM). Acetic acid-induced ulcerative colitis in rat model was chosen to examine the antioxidant potential of the synthesized hybrids (9b and 9f) in the amelioration of ulcerative colitis. Colonic myeloperoxidase and malondialdehyde enzymes were used as biomarkers of anti-ulcerative colitis activity. In the present study, hybrids 9b and 9f reduced the levels of colonic myeloperoxidase and malondialdehyde enzymes significantly (p??0.05) when compared with control (colitic), at a dose (0.03?mM/12.5?mg/kg b.w. p.o.) (50%) less than that of its parent moieties mesalamine (0.16?mM/25?mg/kg) and isatin (0.16?mM/25?mg/kg). Thus, the molecular hybridization was proved to be significant in enhancing the activity of hybrids 9b and 9f by reducing the dose.
- Panga, Shyam,Podila, Naveen Kumar,Ciddi, Veeresham
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p. 956 - 967
(2019/02/14)
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- Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis
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Microtubule affinity-regulating kinase 4 (MARK4) is a potential drug target as the same is found to be over expressed in several types of cancers. In search of effective MARK4 inhibitors, we have synthesized and characterized Isatin-triazole hydrazones (9a-i) and evaluated their inhibitory potential. Of all the compounds, 9g showed better binding affinity and enzyme inhibition potential in sub micromolar range. Human serum albumin (HSA) binding assay suggested an easy transportation of 9g in blood stream due to its binding affinity. In vitro anticancer studies performed on MCF-7, MDA-MB-435s and HepG2 cells using 9g showed inhibition of cell proliferation and cell migration. Further, 9g induces apoptosis in these cancerous cells, with IC50 values of 6.22, 9.94 and 8.14 μM, respectively. Putatively, 9g seems to cause oxidative stress resulting in apoptosis. Functional assay of 9g with a panel of 26 kinases showed MARK4 specific profile. In conclusion, 9g seems to possess an effective inhibitory potential towards MARK4 adding an additional repertoire to anticancer therapeutics.
- Aneja, Babita,Khan, Nashrah Sharif,Khan, Parvez,Queen, Aarfa,Hussain, Afzal,Rehman, Md. Tabish,Alajmi, Mohamed F.,El-Seedi, Hesham R.,Ali, Sher,Hassan, Md. Imtaiyaz,Abid, Mohammad
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p. 840 - 852
(2019/01/04)
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- Synthesis of substituted tryptanthrin via aryl halides and amines as antitumor and anti-MRSA agents
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The natural alkaloid, tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione), and its analogues are found to exhibit potent antitumor and anti-MRSA activities. An efficient and convenient method has been developed for the synthesis of tryptanthrin D-ring derivatives through the reaction of substituted tryptanthrins and secondary amines in moderate to good yields. Some of the new compounds exhibited antitumor activities against the human tumor cell lines A549, HCT116 and MDA-MB-231, with mean IC50 values at low micromolar levels. In addition, some of the compounds showed excellent anti-MRSA activities and were more effective than vancomycin, with MIC values of 0.31–1.25 μg/mL for Mu50,RN4220, and Newman strains.
- Chen, Huan,Hou, Baolong,Liu, Jianli,Liu, Li,Ma, Xiumei,Wang, Cuiling,Wang, Jilin,Wang, Rui,Wang, Yinyin,Zheng, Xudong
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- Organocatalytic Synthesis of Benzazetidines by Trapping Hemiaminals with Protecting Groups
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Benzazetidines are highly strained and inherently unstable heterocycles. There are only few methodologies for assembling these compounds. Here, a protocol is presented to trap an elusive cyclic, four-membered hemiaminal structure. This method affords several benzazetidines in moderate to good yields (up to 81%), and it uses inexpensive materials and does not require catalysts based on transition metals. The high ring strain energy of these benzazetidine systems was estimated by density functional theory calculations to be about 32 kcal mol-1. This synthesis can be applied also on gram scale with reaction yield essentially unchanged.
- Salvio, Riccardo,Placidi, Simone,Sinibaldi, Arianna,Di Sabato, Antonio,Buscemi, Dario C.,Rossi, Andrea,Antenucci, Achille,Malkov, Andrei,Bella, Marco
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p. 7395 - 7404
(2019/06/07)
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- METHOD FOR PRODUCING ISATIN COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for producing an isatin compound useful as raw materials for various medical and agrochemical products and dyes, in high yield, with high purity, at low cost, and by simple operation. SOLUTION: An method for producing an isatin compound includes the reaction of an isonitrosoacetanilide compound represented by formula (1) at 15-60°C with sulfuric acid of 75% or more in concentration [R is H, a halogen atom or a linear/branched/cyclic alkyl group; n is an integer of 1-4]. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0032
(2018/11/10)
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- Design, Synthesis, Characterization, and In Vitro Evaluation of Isatin-Pomalidomide Hybrids for Cytotoxicity against Multiple Myeloma Cell Lines
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Inspired by the concept of molecular hybridization, a series of new isatin-pomalidomide hybrids (9a–9g) were designed, synthesized, characterized, and evaluated for in vitro cytotoxic activity against U266B1 and RPMI 8226 multiple myeloma cell lines. Sandmeyer methodology and N-halomethylketo alkylation reaction are the two important reactions involved in the synthesis of isatin-pomalidomide hybrids (9a–9g). All the synthesized compounds (3a–3d, 4, 5, 6, and 9a–9g) were characterized by using IR, mass, 1H-NMR, and 13C-NMR spectral techniques. The efficacy of all the synthesized compounds was tested against the aforementioned cell lines by employing MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) standard protocols while using pomalidomide as a standard. The test concentrations used in the MTT assay were 1, 10, 20, 30, and 40?μM, and the period of incubation was 24?h. All the synthesized compounds were found to have moderate to greater cytotoxic activity against the aforementioned cell lines. Among them, synthesized hybrids 9f (IC50, U266B1?=?5.15?±?0.72?μM, RPMI8226?=?11.66?±?0.79?μM) and 9g (IC50, U266B1?=?2.50?±?0.37?μM, RPMI8226?=?6.70?±?0.55?μM) displayed better cytotoxic activity against both the cell lines used in the present study.
- Panga, Shyam,Podila, Naveen Kumar,Ciddi, Veeresham
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p. 2919 - 2928
(2018/10/26)
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- Synthesis and cytotoxic studies of novel 5-phenylisatin derivatives and their anti-migration and anti-angiogenic evaluation
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A number of 5-arylisatin derivatives were synthesized in 5–6 steps from readily available starting materials. Their structures were confirmed by 1H NMR and 13C NMR as well as LC/MS. The cytotoxicity of these novel isatins against human leukemia K562 cells were evaluated by MTT assay in vitro. SAR studies indicated that the N-substituted benzyl and C-5 substituted phenyl groups greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 present in the parent ring is required to maintain such a potency. Particularly, N-(p-methoxybenzyl)-5-(p-methoxyphenyl)isatin (compound 2m) showed the highest antitumor activity against K562 cell lines (IC50 = 0.03 μM). Moreover, treatment with compound 2m significantly inhibited liver cancer HepG2 cells proliferation and migration, which could also reduce the human umbilical vein endothelial cells (HUVEC) tube formation. In conclusion, compound 2m exhibited very good cancer cells proliferation inhibition by angiogenesis responses in vitro, and 2m might be a promising angiogenesis inhibitor for cancer treatment.
- Zhang, Qian,Teng, Yuou,Yuan, Yuan,Ruan, Tingting,Wang, Qi,Gao, Xing,Zhou, Yao,Han, Kailin,Yu, Peng,Lu, Kui
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p. 800 - 814
(2018/07/29)
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- Palladium(II)/N-Heterocyclic Carbene Catalyzed One-Pot Sequential α-Arylation/Alkylation: Access to 3,3-Disubstituted Oxindoles
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Rationally designed fluorene-based mono- and bimetallic Pd-PEPPSI complexes were synthesized and demonstrated to be effective for the one-pot sequential α-arylation/alkylation of oxindoles. This streamlined approach offers efficient access to functionalized 3,3-disubstituted oxindoles in excellent yields (up to 89%) under mild reaction conditions.
- Reddy Panyam, Pradeep Kumar,Ugale, Bharat,Gandhi, Thirumanavelan
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supporting information
p. 7622 - 7632
(2018/06/22)
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- NaI-mediated divergent synthesis of isatins and isoindigoes: A new protocol enabled by an oxidation relay strategy
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A new approach for the synthesis of isatins and isoindigoes by an inexpensive and environmentally friendly NaI-mediated transformation is disclosed. The selectivity could be switched by simply varying the solvent, and isatins (using THF) and isoindigoes (using DMSO) could be obtained in moderate to excellent yields.
- Zhang, Hong-Hua,Wang, Yong-Qiang,Huang, Long-Tao,Zhu, Long-Qing,Feng, Yi-Yue,Lu, Ying-Mei,Zhao, Quan-Yi,Wang, Xue-Qiang,Wang, Zhen
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supporting information
p. 8265 - 8268
(2018/07/29)
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- Synthesis of Indoline-2,3-diones by Radical Coupling of Indolin-2-ones with tert-Butyl Hydroperoxide
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A novel strategy has been developed for the synthesis of indoline-2,3-diones through a metal-free radical-coupling reaction. Alkyl radicals derived from indolin-2-ones through a radical-transfer reaction combine with the tert-butylhydroperoxy radical readily generated from commercially available tert-butyl hydroperoxide to afford 3-(tertbutylperoxy)indolin-2-one intermediates that can be further transformed into indoline-2,3-diones under air. This strategy provides a simple and e?cient route to the construction of a C=O bond without the use of any metal catalyst or base.
- Ying, Wei-Wei,Zhu, Wen-Ming,Liang, Hongze,Wei, Wen-Ting
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supporting information
p. 215 - 218
(2017/09/28)
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- Method for preparing indole-2,3-dione derivatives by catalytic oxidation of microwave copper/peroxyacetic acid
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The invention discloses a method for preparing indole-2,3-dione derivatives by catalytic oxidation of microwave copper/peroxyacetic acid. The method comprises the following steps: a catalytic amount of catalyst copper iodide, indole, a derivative of the indole and peroxyacetic acid are added into a reaction vessel, wherein the indole, the derivative of the indole and the peroxyacetic acid are usedas raw materials, ethanol is used as a solvent, the reaction vessel is placed into a microwave reaction instrument, a reaction is performed at certain temperature and power, after a certain time, reduced-pressure concentration is performed, and a product is purified by column chromatography. The method provided by the invention is a method having novel raw materials, simple operation and high efficiency used for preparing a benzimidazole derivative; and compared with the prior art, the method provided by the invention has an obviously-accelerated reaction speed than that under conventional heating, mild reaction conditions, simple operation, a high yield, safety, low costs and environmental protection.
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Paragraph 0024; 0048
(2018/09/08)
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- An efficient synthesis of versatile synthon 3-chlorooxindoles with NaCl/oxone
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The present work describes an expedient approach for the direct conversion of indole-3-carboxaldehyde to 3-chlorooxindoles using a simple sustainable synthetic method. From an environmental perspective, a combination of NaCl/oxone in a CH3CN?:?H2O (1?:?1) system was developed for direct oxidative chlorination of a wide array of indole derivatives. This chlorination strategy is more viable, remarkably cheaper and provides easy access to potential 3-chlorooxindoles. In addition, this environmentally benign method can also be applicable for constructing isatin derivatives in good yields.
- Lakshmi Reddy, Vanammoole,Prathima, Parvathaneni Sai,Rao, Vaidya Jayathirtha,Bikshapathi, Raktani
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p. 20152 - 20155
(2018/12/13)
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- Assessment of 5-substituted Isatin as Surface Recognition Group: Design, Synthesis, and Antiproliferative Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors
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Histone deacetylase (HDAC) is a promising target for cancer treatment. HDAC inhibitors consist of three pharmacophoric features: an aromatic cap group, zinc binding group (ZBG), and a linker chain connecting cap group to ZBG. Herein, we report on (i) substituted isatin moiety as the cap group that recognizes the surface of active enzyme pocket and (ii) thiosemicarbazide moiety incorporated as linker group responsible for connecting the cap group to ZBG (hydroxamic acid). The synthesized compounds were evaluated for their antiproliferative activity and HDAC enzyme inhibition. The binding mode analysis of proposed compounds was evaluated by docking studies. Several analogs were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells, with GI50 values in the micromolar range. One compound (Vd) was found to have greater in vitro antiproliferative activity in comparison to other compounds.
- Singh, Avineesh,Raghuwanshi, Kamlesh,Patel, Vijay K,Jain, Deepak K,Veerasamy, Ravichandran,Dixit, Anshuman,Rajak, Harish
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p. 366 - 374
(2017/09/27)
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- Isatin N,N′-Cyclic Azomethine Imine 1,3-Dipole and Abnormal [3 + 2]-Cycloaddition with Maleimide in the Presence of 1,4-Diazabicyclo[2.2.2]octane
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A new isatin N,N′-cyclic azomethine imine synthon was devised, and an unexpected abnormal [3 + 2]-cycloaddition with maleimide catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) has been disclosed. A variety of tricyclic spiropyrrolidine oxindoles bearing a dinitrogen heterocycle and succinimide scaffold were obtained in excellent yields (up to 96%) and diastereoselectivities (up to 97:3) under mild conditions.
- Wang, Xiao,Yang, Peng,Zhang, Yong,Tang, Chao-Zhe,Tian, Fang,Peng, Lin,Wang, Li-Xin
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supporting information
p. 646 - 649
(2017/02/10)
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- Natural α-methylenelactam analogues: Design, synthesis and evaluation of α-alkenyl-γ and δ-lactams as potential antifungal agents against Colletotrichum orbiculare
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In our continued efforts to improve the potential utility of the α-methylene-γ-lactone scaffold, 62 new and 59 known natural α-methylenelactam analogues including α-methylene-γ-lactams, α-arylidene-γ and δ-lactams, and 3-arylideneindolin-2-ones were synthesized as the bioisosteric analogues of the α-methylenelactone scaffold. The results of antifungal and cytotoxic activity indicated that among these derivatives compound (E)-1-(2, 6-dichlorobenzyl)-3-(2-fluorobenzylidene) pyrrolidin-2-one (Py51) possessed good selectivity with the highest antifungal activity against Colletotrichum orbiculare with IC50?=?10.4?μM but less cytotoxic activity with IC50?=?141.2?μM (against HepG2 cell line) and 161.2?μM (against human hepatic L02?cell line). Ultrastructural change studies performed by transmission electron microscope showed that Py51 could cause important cell morphological changes in C.?orbiculare, such as plasma membrane detached from cell wall, cell wall thickening, mitochondria disruption, a dramatic increase in vacuolation, and eventually a complete loss in the integrity of organelles. Significantly, mitochondria appeared one of the primary targets, as confirmed by their remarkably aberrant morphological changes. Analysis of structure–activity relationships revealed that incorporation of the aryl group into the α-exo-methylene and the N-benzyl substitution increased the activity. Meanwhile, the α-arylidene-γ-lactams have superiority in selectivity over the 3-arylideneindolin-2-ones. Based on the results, the N-benzyl substituted α-(2-fluorophenyl)-γ-lactam was identified as the most promising natural-based scaffold for further discovering and developing improved crop-protection agents.
- Delong, Wang,Lanying, Wang,Yongling, Wu,Shuang, Song,Juntao, Feng,Xing, Zhang
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p. 286 - 307
(2017/03/09)
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- Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups
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As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605?μM, respectively), compound 9n with IC50 values of 0.032, 0.256 and 0.311?μM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity.
- Gao, Shuai,Zang, Jie,Gao, Qianwen,Liang, Xuewu,Ding, Qinge,Li, Xiaoyang,Xu, Wenfang,Chou, C. James,Zhang, Yingjie
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p. 2981 - 2994
(2017/05/25)
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- Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors
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A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50 values of 0.5 and 0.2 μM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization. In addition, immunofluorescence and flow cytometry analysis revealed that selected compounds caused disruption of the mitotic spindle assembly and G2/M phase arrest of the cell cycle, which correlated with proliferation inhibitory activity. Molecular docking analysis demonstrated the interaction of 7b at the colchicine binding site of tubulin. These results indicate these compounds are promising inhibitors of tubulin polymerization for the potent treatment of cancer.
- Zhu, Li,Luo, Kaixiu,Li, Ke,Jin, Yi,Lin, Jun
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p. 5939 - 5951
(2017/10/13)
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- Convenient and Clean Synthesis of Isatins by Metal-Free Oxidation of Oxindoles
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A metal-free synthesis of isatins was achieved through the oxidative reactions of oxindoles with molecular oxygen in the presence of tert -butyl nitrite as an additive. This strategy provides a convenient and simple synthetic route to the construction of C=O bonds without the need for any catalyst or base. The attractive features of this reaction include its convenient procedure and mild reaction conditions.
- Wei, Wen-Ting,Ying, Wei-Wei,Zhu, Wen-Ming,Wu, Yi,Huang, Yi-Ling,Cao, Yi-Qi,Wang, Yi-Ning,Liang, Hongze
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supporting information
p. 2307 - 2310
(2017/10/06)
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- 3-(morpholine substituted aromatic imido) indole compound, preparation method thereof and application
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The invention provides a 3-(morpholine substituted aromatic imido) indole compound which is simple in structure and simple and convenient in synthesis method. In activity tests, some compounds show a certain anti-Kv1.5 biological activity and selectivity, the compound T16 shows high inhibition ratio (IR=70.8%) at the level of 100 micrometers, and the compound T5 also shows a certain inhibitory activity (IR=57.5%) at the level of 100 micrometers. Besides, the compound has a certain target selectivity for a Kv1.5 channel. The invention further provides a preparation method of the 3-(morpholine substituted aromatic imido) indole compound and an application of the compound to preparation, design and development of atrial fibrillation treating medicines.
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Paragraph 0050; 0051; 0052; 0053
(2017/09/05)
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- Iodosobenzoic Acid (IBA) Catalysed Benzylic and Aromatic C–H Oxidations
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Abstract: A metal-free reusable hypervalent iodine(III) reagent is employed as a stable catalyst for the selective oxidation of active methylenes, indoles and styrene C–H bond to corresponding carbonyl compounds. From both economic and environmental point of view use of 2-Iodosobenzoic acid for oxidations replacing metals, makes the reaction interesting. Graphical Abstract: A metal-free reusable hypervalent iodine(III) reagent is employed as a stable catalyst for the selective oxidation of active methylenes, Indoles and styrene C–H bond to corresponding carbonyl compounds. From both an economic and environmental point of view use of oxygen as the oxidant, makes the reaction interesting. [Figure not available: see fulltext.].
- Bindu, Vittam Hima,Parvathaneni, Sai Prathima,Rao, Vaidya Jayathirtha
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p. 1434 - 1440
(2017/05/19)
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- Preparation method of indoledione compound
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The invention provides a preparation method of an indoledione compound. The method comprises the following steps: reacting an arylalkynyl compound of formula (I) with amine in an organic solvent in the presence of an oxidant, a catalyst and a ligand to obtain an acetaldehyde amide compound, and preparing the indoledione compound from the acetaldehyde amide under the action of hydrochloric acid. The method has the advantages of realization of high-yield synthesis of the indoledione compound, good application prospect and good industrial production potential.
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Paragraph 0040
(2017/08/30)
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- Design, synthesis and apoptosis inducing effect of novel (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)-benzylidene)indolin-2-ones as potential antitumour agents
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A series of new (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)benzylidene)indolin-2-one derivatives has been synthesized and evaluated for their cytotoxic activity against selected human cancer cell lines of prostate (PC-3 and DU-145), breast (BT-549 and MDA-MB-231) and non-tumorigenic prostate epithelial cells (RWPE-1). Among the tested, one of the compounds 4p exhibited potent cytotoxicity selectively on prostate cancer cell lines (PC-3 and DU-145; IC50: 1.89 ± 0.6 and 1.94 ± 0.2 μM, respectively). Further experiments were conducted with 4p on PC-3 cancer cells to study the mechanisms of growth inhibition and apoptosis inducing effect. Treatment of PC-3 cells with test compound 4p resulted in inhibition of cell migration through disorganization of F-actin protein. The flow-cytometry analysis results showed that the compound arrested PC-3 cancer cells in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining and annexin-V binding assay revealed that the compound 4p inhibited tumor cell proliferation through induction of apoptosis. Western blot studies demonstrated that the compound 4p treatment led to activation of caspase-3, increased expression of pro-apoptotic Bax and significantly decreased expression of anti-apoptotic Bcl-2 in human prostate cancer PC-3 cells. In addition, the mitochondrial membrane potential (ΔΦm) was also affected and the levels of intracellular Ca2+ were raised.
- Senwar, Kishna Ram,Reddy, T. Srinivasa,Thummuri, Dinesh,Sharma, Pankaj,Naidu,Srinivasulu, Gannoju,Shankaraiah, Nagula
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- Design and synthesis of 4′-O-alkylamino-tethered-benzylideneindolin-2-ones as potent cytotoxic and apoptosis inducing agents
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A series of new 4′-O-alkylamino-tethered-benzylideneindolin-2-one derivatives has been synthesized and evaluated for their anti-proliferative activity against selected human cancer cell lines of lung (A549), prostate (DU-145), breast (BT549 and MDA-MB-231) and normal breast epithelial cells (MCF-10A). Gratifyingly, the compounds 5j, 5o and 5r exhibited potent cytotoxicity against breast cancer cell lines (BT549 and MDA-MB-231) with IC50values in the range of 1.26–2.77?μM, and are found to be safer with lesser cytotoxicity on normal breast epithelial cells (MCF-10A). Further, experiments were conducted with these compounds 5j, 5o and 5r on MDA-MB-231 cancer cells to study the mechanism of growth inhibition and apoptosis inducing effect. Treatment of MDA-MB-231 cells with test compounds resulted in inhibition of cell migration through disorganization and disruption of F-actin capping protein. The flow-cytometry analysis results showed that the compound 5o arrested MDA-MB-231 cells in G0/G1 phase of cell cycle in a dose dependent manner. Hoechst staining study revealed that the test compounds inhibited tumor cell proliferation through induction of apoptosis. In addition, the mitochondrial membrane potential (DΨm) was affected and the increased level of reactive oxygen species (ROS) was noted in MDA-MB-231 cells.
- Senwar, Kishna Ram,Reddy, T. Srinivasa,Thummuri, Dinesh,Sharma, Pankaj,Bharghava, Suresh K.,Naidu,Shankaraiah, Nagula
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p. 4061 - 4069
(2016/08/01)
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- New (E)-1-alkyl-1H-benzo[d]imidazol-2-yl)methylene)indolin-2-ones: Synthesis, in vitro cytotoxicity evaluation and apoptosis inducing studies
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A new series of (E)-benzo[d]imidazol-2-yl)methylene)indolin-2-one derivatives has been synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines of prostate (PC-3 and DU-145) and breast (BT-549, MDA-MB-231, MCF-7, 4T1), non-small lung (A549) and gastric (HGC) cancer cells along with normal breast epithelial cells (MCF10A). Among the tested compounds, 8l showed significant cytotoxic activity against MDA-MB-231 and 4T1 cancer cells with IC50values of 3.26 ± 0.24 μM and 5.96 ± 0.67 μM respectively. The compounds 8f, 8i, 8l and 8o were also screened on normal human breast epithelial cells (MCF10A) and found to be safer with lesser cytotoxicity. The treatment of MDA-MB-231 cells with 8l led to inhibition of cell migration ability through disruption of F-actin protein assembly. The flow-cytometry analysis reveals that the cells arrested in G0/G1 phase of the cell cycle. Further, the compound 8l induced apoptosis of MDA-MB-231 cells was characterized by different staining techniques such as Acridine Orange/Ethidium Bromide (AO/EB), DAPI, annexin V-FITC/PI, Rhodamine-123 and MitoSOX red assay. Western blot studies demonstrated that the compound 8l treatment led to activation of caspase-3, increased expression of cleaved PARP, increased expression of pro-apoptotic Bax and decreased expression of anti-apoptotic Bcl-2 in MDA-MB-231 cancer cells.
- Sharma, Pankaj,Thummuri, Dinesh,Reddy, T. Srinivasa,Senwar, Kishna Ram,Naidu,Srinivasulu, Gannoju,Bharghava, Suresh K.,Shankaraiah, Nagula
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p. 584 - 600
(2016/07/22)
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- Design, synthesis, and biological evaluation of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives as anti-proliferative agents through ROS-induced cell apoptosis
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A novel class of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives were designed and synthesized as potent anti-proliferative agents. Most of these compounds showed potent anti-proliferative activity against some tumor cell lines, including SK-BR-3, MDA-MB-231, HCT-116, SW480, Ovcar-3, HL-60, Saos-2 and HepG2. Compounds 8c and 11h were identified as the most potent ones, while HL-60, HCT116 and MDA-MB-231 were the most sensitive cell lines. Mechanistic study revealed that compound 8c enhanced reactive oxygen species level by inhibiting TrxR and then induced apoptosis by activating apoptosis proteins, bax and cleaved-caspase 3 in HCT116?cells. Preliminary SAR analysis indicated that modifications of the double bond and ester group made great effects on the anti-proliferative activity. Our findings suggested that it was worth further studies on the antitumor potency of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetates.
- Song, Zhuang,Chen, Cai-Ping,Liu, Jun,Wen, Xiaoan,Sun, Hongbin,Yuan, Haoliang
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p. 809 - 819
(2016/09/23)
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- Design, synthesis and antiproliferative activity of novel benzothiazole derivatives conjugated with semicarbazone scaffold
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Two series of novel benzothiazole derivatives conjugated with semicarbazone scaffold were designed and synthesized through a structure-based molecular hybridization strategy. All the target compounds were evaluated for their cytotoxicity in vitro against three cancer cell lines (HT-29, MKN-45 and H460) by standard MTT assay. The pharmacological results indicated that seven compounds (17h-n) exhibited comparable or even better antiproliferative activity in comparison with reference drugs Sorafenib and PAC-1. Particularly, compound 17i displayed remarkable cytotoxicity against tested three cancer cell lines with IC50 values of 0.84, 0.06 and 0.52 μM, which were 4.3-, 36.6-, 4.2-folds more potent than Sorafenib and 1.2-, 13.7-, 6.9-times more active than PAC-1, respectively.
- Bao, Guanglong,Du, Baoquan,Ma, Yuxiu,Zhao, Meng,Gong, Ping,Zhai, Xin
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p. 489 - 498
(2016/07/19)
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- Synthesis and anti-cancer activity evaluation of 5-(2-carboxyethenyl)-isatin derivatives
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A series of novel di- or trisubstituted isatin derivatives were designed and synthesized in 5–6 steps in 25–45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of the fourty-three new isatin derivatives against human T lymphocyte cells Jurkat was evaluated by MTT assay in vitro. SAR study suggested that the combination of 1-benzyl and 5-[trans-2-(methoxycarbonyl)ethen-1-yl] substitution greatly enhanced their cytotoxic activity. Among them, compound 2h was shown to have a significant cytotoxic activity with an IC50 value of 0.03 μM, more than 330-fold higher than that of it's mother molecule isatin. Investigation of the cell morphology changes and annexin-V/PI staining study demonstrated that compound 2h inhibited the proliferation of Jurkat cells by inducing apoptosis. Since compound 2h induced the dissipation of mitochondrial membrane potential and the activation of caspase-3, it was obvious that compound 2h inhibited the proliferation of Jurkat cells through the mitochondrial apoptotic pathway. Other than this, compound 2h exerted inhibition effect to many other tumor cells and only showed weak cytotoxic to human normal cells suggesting that compound 2h possessed a broad range of anticancer spectrum and high safety to normal cells.
- Teng, Yu-Ou,Zhao, Hong-Ye,Wang, Jing,Liu, Huan,Gao, Mei-Le,Zhou, Yao,Han, Kai-Lin,Sun, Hua,Yu, Peng,Fan, Zhen-Chuan,Zhang, Yong-Min
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p. 145 - 156
(2018/05/02)
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- Synthesis of diverse isatins: Via ring contraction of 3-diazoquinoline-2,4-diones
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An efficient synthesis of diverse isatin derivatives was accomplished by a copper-mediated reaction of 3-diazoquinoline-2,4-diones via ring contraction through domino Wolff rearrangement, decarboxylation, bromination, substitution, and dehydration. This protocol has several advantages as a one-pot procedure, with functional group tolerance, and high yield.
- Shrestha, Rajeev,Lee, Gun Joon,Lee, Yong Rok
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p. 63782 - 63787
(2016/07/19)
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- A Benzisoelenazolone modified pyrrole methyl ester substituted indole ketone compound and use thereof
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The invention discloses a benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound and a use thereof. The invention depends on and claims the priority of a Chinese patent application 201110105248.0 submitted on April 26, 2011. Through reference, all contents of the Chinese patent application 201110105248.0 are incorporated into the invention. The benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound is shown in the general formula I. The 2-indolone compound provided by the invention has excellent antitumor activity and can be widely used for preparation of antitumor drugs.
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Paragraph 0113-0114; 0134-0136
(2016/10/08)
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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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- Imidazolidinone based chiral auxiliary mediated acetate aldol reactions of isatin derivatives and stereoselective synthesis of 3-substituted-3-hydroxy-2-oxindoles
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Acetate aldol reactions of (S)-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one chiral auxiliary have been optimized with high yields and diastereoselectivity on various N-substituted isatins. The standardized reaction condition was employed for the stereoselective synthesis of furoindolines, and the pyrroloindole based natural products flustraminol B and N-benzyl alline.
- Gangar, Mukesh,Kashyap, Naresh,Kumar, Kapil,Goyal, Sandeep,Nair, Vipin A.
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p. 7074 - 7081
(2015/12/01)
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- A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: Construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters
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A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has been successfully developed to afford the highly congested bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to 91%), excellent diastereoselectivities (up to >20 : 1 dr), and good enantioselectivities (up to 98% ee). Some synthetic transformations of the reaction products were also studied.
- Gui, Yong-Yuan,Yang, Jian,Qi, Liang-Wen,Wang, Xiao,Tian, Fang,Li, Xiao-Nian,Peng, Lin,Wang, Li-Xin
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supporting information
p. 6371 - 6379
(2015/06/08)
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- 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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- Design and synthesis of 3-substituted indolin-2-one derivatives with methyl (e)-2-(3-Methoxy) acrylate moiety
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In this article, fifteen indolin-2-one derivatives with methyl (E)-2-(3-methoxy)acrylate group were designed and synthesized. The structures of target compounds were confirmed by 1H NMR, IR and HR-MS spectra analysis.
- Luo, Xi,Zhang, Yi-Ying,Wang, Yu-Liang
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p. 2911 - 2916
(2015/12/11)
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- Synthesis of isatin derivatives under metal free conditions using hypervalent iodine
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Hypervalent iodine(III)/TEMPO-mediated C(sp3), C(sp2) C-H bond oxidation of different oxindole and indole derivatives to their corresponding isatin derivatives was successfully achieved with excellent yields at room temperature. This metal-free method provides a direct access to potential synthon isatin that could be applied in the total synthesis of several biologically active natural products.
- Sai Prathima, Parvathaneni,Bikshapathi, Raktani,Rao, Vaidya Jayathirtha
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p. 6385 - 6388
(2015/11/16)
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- Copper-catalyzed base-accelerated direct oxidation of C-H bond to synthesize benzils, isatins, and quinoxalines with molecular oxygen as terminal oxidant
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We describe herein an efficient and general copper (II)-catalyzed base-accelerated oxidation of the C-H bond to synthesize benzils and isatins. With similar oxidation system an efficient one-pot procedure for the synthesis of quinoxaline derivatives was realized. The two protocols feature using molecular oxygen as terminal oxidant, low catalyst loading, wide substrate scope, and high functional-group tolerance.
- Yu, Jing-Wen,Mao, Shuai,Wang, Yong-Qiang
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supporting information
p. 1575 - 1580
(2015/03/14)
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- Synthesis and structure-activity relationship studies of small molecule disruptors of EWS-FLI1 interactions in Ewing's sarcoma
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EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing's sarcoma family tumors (ESFT). Using our previously reported lead compound 2 (YK-4-279), we designed and synthesized a focused library of analogues. The functional inhibition of the analogues was measured by an EWS-FLI1/NR0B1 reporter luciferase assay and a paired cell screening approach measuring effects on growth inhibition for human cells containing EWS-FLI1 (TC32 and TC71) and control PANC1 cell lines devoid of the oncoprotein. Our data revealed that substitution of electron donating groups at the para-position on the phenyl ring was the most favorable for inhibition of EWS-FLI1 by analogs of 2. Compound 9u (with a dimethylamino substitution) was the most active inhibitor with GI50 = 0.26 ± 0.1 μM. Further, a correlation of growth inhibition (EWS-FLI1 expressing TC32 cells) and the luciferase reporter activity was established (R2 = 0.84). Finally, we designed and synthesized a biotinylated analogue and determined the binding affinity for recombinant EWS-FLI1 (Kd = 4.8 ± 2.6 μM).
- Tosso, Perrer N.,Kong, Yali,Scher, Lauren,Cummins, Ryan,Schneider, Jeffrey,Rahim, Said,Holman, K. Travis,Toretsky, Jeffrey,Wang, Kan,üren, Aykut,Brown, Milton L.
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p. 10290 - 10303
(2015/02/19)
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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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- Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents
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Forty four di- or trisubstituted novel isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of these new isatin derivatives against three human tumor cell lines, K562, HepG2 and HT-29, were evaluated by MTT assay in vitro. SAR studies suggested that the combination of 1-benzyl and 5-[trans-2- (methoxycarbonyl)ethen-1-yl] substitution greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 as present in the parent ring is required to such a potency. This study leads to the identification of two highly active molecules, compounds 2h (IC50 = 3 nM) and 2k (IC50 = 6 nM), against human leukemia K562 cells.
- Han, Kailin,Zhou, Yao,Liu, Fengxi,Guo, Qiannan,Wang, Pengfei,Yang, Yao,Song, Binbin,Liu, Wei,Yao, Qingwei,Teng, Yuou,Yu, Peng
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supporting information
p. 591 - 594
(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 and biological evaluation of 5′-phenyl-3′H-spiro- [indoline-3,2′-[1,3,4]oxadiazol]-2-one analogs
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A series of 5′-phenyl-3′H-spiro[indoline-3,2′-[1,3,4] thiadiazol]-2-one analogs were synthesized and their Bcl-2 protein inhibitory activities were studied. The lead compound was originally identified using a fluorescence polarization-based competitive binding assay. Among the 10 compounds investigated, 1k showed good binding affinities to Bcl-xL and Mcl-1, with inhibition constants of 8.9 μmol/L and 3.4 μmol/L, respectively. While compound 1c achieved tight binding affinities to Bcl-xL (Ki = 0.16 μmol/L), has the potential to be a new lead compound.
- Liu, Hua-Quan,Wang, De-Cai,Wu, Fei,Tang, Wei,Ouyang, Ping-Kai
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p. 929 - 933
(2013/09/24)
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- Synthesis and biological evaluation of 2-(5-substituted-1-((diethylamino) methyl)-2-oxoindolin-3-ylidene)-N-substituted-hydrazinecarbothioamides
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Various 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene) hydrazinecarbothioamide (4a, b) and 5-substituted-2-(1-((diethylamino)methyl)-2- oxoindolin-3-ylidene)-N-(phenyl-4-substituted)hydrazinecarbothioamide (5a-h) derivatives were synthesized. The compounds were screened for cytotoxicity against human HeLa and CEM T-lymphocytes as well as murine L1210 cells. The compounds were also screened for β-lactamase inhibitory activity, antiviral, antibacterial, and antifungal activity against various strains of microorganisms. Several of these compounds were endowed with low micromolar 50 %-cytostatic concentration (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells (L1210) were also the most inhibitory against human T-lymphocyte (CEM) tumor cells. Derivative 2-(1-((diethylamino)methyl)-2-oxoindolin-3- ylidene)-N-(4-methoxyphenyl)hydrazinecarbothioamide 5c emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC50 11-20 μM). Moderate antimicrobial activity was observed for all derivatives. The encouraging cytostatic and antiviral activity data provide an adequate rationale for further modification of these molecular scaffolds. Graphical abstract: Derivative 5c (1.9-4.4 μM) emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC50 11-20 μM). [Figure not available: see fulltext.]
- Karki, Subhas S.,Kulkarni, Amol A.,Kumar, Sujeet,Veliyath, Suresh Kumar,De Clercq, Erik,Balzarini, Jan
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p. 2014 - 2022
(2013/07/26)
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