- An Expedient Process for the Synthesis of 2-(N -Arylamino)benzaldehydes from 2-Hydroxybenzaldehydes via Smiles Rearrangement
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This paper describes an efficient Smiles rearrangement process for the synthesis of 2-(N-arylamino)benzaldehyde derivatives with reasonable yields. A mechanism is proposed for the reaction course. Georg Thieme Verlag Stuttgart, New York.
- Saeidian, Hamid,Mirjafary, Zohreh,Abdolmaleki, Elinaz,Moradnia, Farzaneh
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- Synthesis and luminescence properties of salicylaldehyde isonicotinoyl hydrazone derivatives and their europium complexes
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Four novel salicylaldehyde isonicotinoyl hydrazone derivatives and their corresponding europium ion complexes were synthesized and characterized, while the luminescence properties and the fluorescence quantum yields of the target complexes were investigated. The results indicated that the ligands favored energy transfers to the emitting energy level of europium ion, and four target europium complexes showed the characteristic luminescence of central europium ion. Besides the luminescence intensity of the complex with methoxy group, which possessed the highest fluorescence quantum yield (0.522), was stronger than that of other complexes. Furthermore, the electrochemical properties of the target complexes were further investigated by cyclic voltammetry, the results indicated that the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) energy levels and the oxidation potential of the complexes with electron donating group increased, however, that of the complexes with accepting electron group decreased.
- Shan, Wenfei,Liu, Fen,Liu, Jiang,Chen, Yanwen,Yang, Zehui,Guo, Dongcai
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- Design, synthesis, docking study, α-glucosidase inhibition, and cytotoxic activities of acridine linked to thioacetamides as novel agents in treatment of type 2 diabetes
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A novel series of acridine linked to thioacetamides 9a–o were synthesized and evaluated for their α-glucosidase inhibitory and cytotoxic activities. All the synthesized compounds exhibited excellent α-glucosidase inhibitory activity in the range of IC50 = 80.0 ± 2.0–383.1 ± 2.0 μM against yeast α-glucosidase, when compared to the standard drug acarbose (IC50 = 750.0 ± 1.5 μM). Among the synthesized compounds, 2-((6-chloro-2-methoxyacridin-9-yl)thio)-N-(p-tolyl) acetamide 9b displayed the highest α-glucosidase inhibitory activity (IC50 = 80.0 ± 2.0 μM). The in vitro cytotoxic assay of compounds 9a–o against MCF-7 cell line revealed that only the compounds 9d, 9c, and 9n exhibited cytotoxic activity. Cytotoxic compounds 9d, 9c, and 9n did not show cytotoxic activity against the normal human cell lines HDF. Kinetic study revealed that the most potent compound 9b is a competitive inhibitor with a Ki of 85 μM. Furthermore, the interaction modes of the most potent compounds 9b and 9f with α-glucosidase were evaluated through the molecular docking studies.
- Mohammadi-Khanaposhtani, Maryam,Rezaei, Sepideh,Khalifeh, Reza,Imanparast, Somaye,Faramarzi, Mohammad Ali,Bahadorikhalili, Saeed,Safavi, Malihe,Bandarian, Fatemeh,Nasli Esfahani, Ensieh,Mahdavi, Mohammad,Larijani, Bagher
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- Reaction of Silyl Enol Ethers with N-Chlorosuccinimide: Trapping the Siloxycarbinyl Cation by an Azide Anion
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Reaction of silyl enol ethers (1a-1f) with N-chlorosuccinimide afforded siloxycarbinyl cations which were trapped by nucleophiles (NaN3 and MeOH); subsequebt rearrangement of the azido products (2a,b,d,e-N3) under reflux in decalin led to anilide derivatives (3a,b,d,e).
- Ohkata, Katsuo,Mase, Mikiko,Akiba, Kin-ya
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- Synthesis and luminescence properties of 1,3,4-oxadiazole acetamide derivatives and their rare earth complexes
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A series of 1,3,4-oxadiazole acetamide derivatives have been designed and synthesized, and their complexes with Eu(III) and Tb(III) were also prepared. The luminescence properties of the target complexes were investigated, and the results indicated that a
- Zhang, Wu,He, Wei,Guo, Xiaorui,Chen, Yanwen,Wu, Limin,Guo, Dongcai
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- Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic screening with potential apoptosis-inducing activity
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Two novel series including Schiff bases of the pyrrolizine-5-carboxamides and their Cu(II) complexes were designed, synthesized and analysed using spectral and analytical techniques. The analytical results indicated the formation of the complexes in 1:1 o
- Gouda, Ahmed M.,El-Ghamry, Hoda A.,Bawazeer, Tahani M.,Farghaly, Thoraya A.,Abdalla, Ashraf N.,Aslam, Akhmed
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- Optimization of pyrrolizine-based Schiff bases with 4-thiazolidinone motif: Design, synthesis and investigation of cytotoxicity and anti-inflammatory potency
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Two new series of pyrrolizine-5-carboxamides were synthesized and evaluated for their anticancer and anti-inflammatory activities. The new compounds exhibited potent cytotoxicity (IC50 = 0.10–22.96 μM) against three cancer (MCF-7, A2780 and HT2
- Shawky, Ahmed M.,Abourehab, Mohammed A.S.,Abdalla, Ashraf N.,Gouda, Ahmed M.
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- Synthesis of Novel 6-Mercapto-12-phenethyl-quinazolino[3,4-a]quinazolinones
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Novel 6-mercapto-12-phenethyl-quinazolino[3,4-a]quinazolinone derivatives were synthesized through a user-friendly five-step reaction starting from isatoic anhydride. All products were characterized by IR,1H-NMR,13C-NMR spectroscopy, and chemical analysis. All of them were evaluated for their in vitro cytotoxic activity against two cell lines namely MOLT-4 (human lymphoblastic leukemia) and MCF-7 (human breast adenocarcinoma).
- Mohammadhosseini, Negar,Moradi, Shahram,Khoobi, Mehdi,Shafiee, Abbas
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- Synthesis, characterization and properties of salicylhydrazide-salicylacylhydrazone derivatives and their terbium complexes
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A series of terbium complexes with salicylhydrazide-salicylacylhydrazone derivatives were synthesized and characterized by elemental analysis, IR spectra, UV/vis spectra and thermal analysis. The luminescence and electrochemical properties of the terbium complexes were investigated. The results show that all the target complexes exhibited characteristic emissions of terbium ions and the complex substituted by the chlorine has the strongest luminescence intensity with the highest quantum yield at 0.609. The introduction of donating electron groups could increase the oxidation potential and the highest occupied molecular orbital energy level of the terbium complex; however, the introduction of accepting electron groups gave the opposite result.
- Meng, Defen,Liu, Fen,Li, Yingying,Yang, Zehui,Li, Guizhi,Guo, Dongcai
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- Piperidine derivatives as nonprostanoid IP receptor agonists 2
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We searched for a strong and selective nonprostanoid IP agonist bearing piperidine and benzanilide moieties. Through optimization of substituents on the benzanilide moiety, the crucial part of the agonist, 43 (2-((1-(2-(N-(4-tolyl)benzo[d][1,3]dioxole-5-c
- Hayashi, Ryoji,Ito, Hiroaki,Ishigaki, Takeshi,Morita, Yasuhiro,Miyamoto, Mitsuko,Isogaya, Masafumi
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- Novel pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety: design, synthesis, molecular docking, and biological evaluation as potential multi-target cytotoxic agents
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In the present study, two new series of pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety were designed, synthesised, and evaluated for their cytotoxic activity. The benzamide derivatives 16a–e showed higher cytotoxicity than their corresponding Schiff b
- Shawky, Ahmed M.,Ibrahim, Nashwa A.,Abdalla, Ashraf N.,Abourehab, Mohammed A. S.,Gouda, Ahmed M.
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- Inhibition of Autophagy by a Small Molecule through Covalent Modification of the LC3 Protein
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The autophagic ubiquitin-like protein LC3 functions through interactions with LC3-interaction regions (LIRs) of other autophagy proteins, including autophagy receptors, which stands out as a promising protein–protein interaction (PPI) target for the intervention of autophagy. Post-translational modifications like acetylation of Lys49 on the LIR-interacting surface could disrupt the interaction, offering an opportunity to design covalent small molecules interfering with the interface. Through screening covalent compounds, we discovered a small molecule modulator of LC3A/B that covalently modifies LC3A/B protein at Lys49. Activity-based protein profiling (ABPP) based evaluations reveal that a derivative molecule DC-LC3in-D5 exhibits a potent covalent reactivity and selectivity to LC3A/B in HeLa cells. DC-LC3in-D5 compromises LC3B lipidation in vitro and in HeLa cells, leading to deficiency in the formation of autophagic structures and autophagic substrate degradation. DC-LC3in-D5 could serve as a powerful tool for autophagy research as well as for therapeutic interventions.
- Chen, Kaixian,Chen, Zhifeng,Dang, Yongjun,Ding, Hong,Fan, Shijie,Hu, Junchi,Jiang, Hualiang,Li, Lianchun,Li, Quanfu,Lin, Tingting,Lu, Junyan,Luo, Cheng,Otomo, Chinatsu,Otomo, Takanori,Tan, Minjia,Tao, Hongru,Wan, Wei,Wen, Yi,Xie, Yuli,Xu, Pan,Yao, Zhiyi,Yue, Liyan,Zhang, Bidong,Zhang, Naixia,Zhang, Yuanyuan,Zhou, Bing,Zhu, Mingrui
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supporting information
p. 26105 - 26114
(2021/11/09)
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- Discovery of new indole-based 1,2,4-triazole derivatives as potent tubulin polymerization inhibitors with anticancer activity
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Thirty-six novel indole-based 1,2,4-triazole derivatives were designed and synthesized through the molecular hybrid strategy. The bioassay results revealed that 9p displayed excellent antiproliferative efficacies in the nanomolar range against HeLa cells. Importantly, the compound exhibited no obvious cytotoxic activity (IC50 > 100 μM) toward HEK-293, a normal human embryonic kidney cell line. Mechanism analysis indicated that 9p significantly arrested the cell cycle at the G2/M phase and induced apoptosis in HeLa cells in a dose-dependent manner. Further evidence demonstrated that the promising compound effectively inhibited tubulin polymerization with an IC50 value of 8.3 μM, and molecular docking studies revealed that 9p well occupied the colchicine-site in tubulin. The present study highlights that indole-triazole hybrids might be used as a promising scaffold to develop novel tubulin polymerization inhibitors for cancer treatment.
- Chen, Lin,Jian, Xie-Er,Liu, Yu-Xia,Ma, Yu-Feng,Yang, Fang,You, Wen-Wei,Zhao, Pei-Liang
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p. 21869 - 21880
(2021/12/09)
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- N-Aryl mercaptoacetamides as potential multi-target inhibitors of metallo-β-lactamases (MBLs) and the virulence factor LasB fromPseudomonas aeruginosa
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Increasing antimicrobial resistance is evolving to be one of the major threats to public health. To reduce the selection pressure and thus to avoid a fast development of resistance, novel approaches aim to target bacterial virulence instead of growth. Another strategy is to restore the activity of antibiotics already in clinical use. This can be achieved by the inhibition of resistance factors such as metallo-β-lactamases (MBLs). Since MBLs can cleave almost all β-lactam antibiotics, including the “last resort” carbapenems, their inhibition is of utmost importance. Here, we report on the synthesis andin vitroevaluation ofN-aryl mercaptoacetamides as inhibitors of both clinically relevant MBLs and the virulence factor LasB fromPseudomonas aeruginosa. All testedN-aryl mercaptoacetamides showed low micromolar to submicromolar activities on the tested enzymes IMP-7, NDM-1 and VIM-1. The two most promising compounds were further examined in NDM-1 expressingKlebsiella pneumoniaeisolates, where they restored the full activity of imipenem. Together with their LasB-inhibitory activity in the micromolar range, this class of compounds can now serve as a starting point for a multi-target inhibitor approach against both bacterial resistance and virulence, which is unprecedented in antibacterial drug discovery.
- Brunst, Steffen,Ducho, Christian,Frank, Denia,Hirsch, Anna K. H.,Kramer, Jan S.,Proschak, Ewgenij,Rotter, Marco,Voos, Katrin,Weizel, Lilia,Wichelhaus, Thomas A.,Yahiaoui, Samir,Haupenthal, J?rg
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supporting information
p. 1698 - 1708
(2021/11/23)
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- Antidiabetic compounds
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Compounds for the treatment of hyperglycemia and/or diabetes are provided. The compounds, which inhibit the enzyme dipeptidyl peptidase (DPP-4), are based on the structure where X may be present or absent an may be OH, Ar is an aryl group; and n ranges from 0 to 5.
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Page/Page column 13-14
(2020/06/16)
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- Thiazole amide compound as well as preparation and application thereof
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The invention discloses a thiazole amide compound as well as preparation and application thereof. The structural general formula of the thiazole amide compound is shown in the specification, wherein an X group is selected from methylene (-CH2-), oxygen (O), amino (-NH), N-methyl (-NCH3-), N-isopropyl (-N-CH (CH3) 2) and sulfur (S), and the R group is selected from phenyl, p-methylphenyl, p-nitrophenyl, p-fluorophenyl, p-hydroxyphenyl, p-methoxyphenyl, 3-chloro-2-methylphenyl and 5-chloro-2-methylphenyl. The thiazole amide compound disclosed by the invention has excellent antibacterial activityon valsa mali, fusarium oxysporum, colletotrichum citri and the like, and can be used for preventing and treating crop diseases.
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Paragraph 0007-0008
(2020/08/02)
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- Design, synthesis and biological evaluation of novel naturally-inspired multifunctional molecules for the management of Alzheimer's disease
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In our overall goal to overcome the limitations associated with natural products for the management of Alzheimer's disease and to develop in-vivo active multifunctional cholinergic inhibitors, we embarked on the development of ferulic acid analogs. A systematic SAR study to improve upon the cholinesterase inhibition of ferulic acid with analogs that also had lower logP was carried out. Enzyme inhibition and kinetic studies identified compound 7a as a lead molecule with preferential acetylcholinesterase inhibition (AChE IC50 = 5.74 ± 0.13 μM; BChE IC50 = 14.05 ± 0.10 μM) compared to the parent molecule ferulic acid (% inhibition of AChE and BChE at 20 μM, 15.19 ± 0.59 and 19.73 ± 0.91, respectively). Molecular docking and dynamics studies revealed that 7a fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Asp74, Trp286, and Tyr337 in AChE and with Tyr128, Trp231, Leu286, Ala328, Phe329, and Tyr341 in BChE. Compound 7a was found to be an efficacious antioxidant in a DPPH assay (IC50 = 57.35 ± 0.27 μM), and it also was able to chelate iron. Data from atomic force microscopy images demonstrated that 7a was able to modulate aggregation of amyloid β1-42. Upon oral administration, 7a exhibited promising in-vivo activity in the scopolamine-induced AD animal model and was able to improve spatial memory in cognitive deficit mice in the Y-maze model. Analog 7a could effectively reverse the increased levels of AChE and BChE in scopolamine-treated animals and exhibited potent ex-vivo antioxidant properties. These findings suggest that 7a can act as a lead molecule for the development of naturally-inspired multifunctional molecules for the management of Alzheimer's and other neurodegenerative disorders.
- Chittiboyina, Amar G.,Doerksen, Robert J.,Modi, Gyan,Nayak, Prasanta Kumar,Pandey, Amruta,Pandey, Pankaj,Priya, Khushbu,Rai, Geeta,Shankar, Gauri,Singh, Yash Pal,Tej, Gullanki Naga Venkata Charan,Vishwakarma, Swati
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- Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors
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ABTRACT: In this paper, a new series of isatin-sulphonamide based derivatives were designed, synthesised and evaluated as caspase inhibitors. The compounds containing 1-(pyrrolidinyl)sulphonyl and 2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl substitution at C5 position of isatin core exhibited better results compared to unsubstituted derivatives. According to the results of caspase inhibitory activity, compound 20d showed moderate inhibitory activity against caspase-3 and ?7 in?vitro compared to Ac-DEVD-CHO (IC50 = 0.016 ± 0.002 μM). Among the studied compounds, some active inhibitors with IC50s in the range of 2.33–116.91 μM were identified. The activity of compound 20d was rationalised by the molecular modelling studies exhibiting the additional van der Waals interaction of N-phenylacetamide substitution along with efficacious T-shaped π-π and pi-cation interactions. The introduction of compound 20d with good caspase inhibitory activity will help researchers to find more potent agents.
- Firoozpour, Loghman,Gao, Lixin,Moghimi, Setareh,Pasalar, Parvin,Davoodi, Jamshid,Wang, Ming-Wei,Rezaei, Zahra,Dadgar, Armin,Yahyavi, Hoda,Amanlou, Massoud,Foroumadi, Alireza
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p. 1674 - 1684
(2020/09/02)
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- Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
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Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
- Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
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- Synthesis, in silico Study and Antimicrobial Evaluation of New Selenoglycolicamides
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Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were fully characterized by elemental analysis, infrared (IR),1H and13C nuclear magnetic resonance (NMR). The compounds were evaluated in an i
- Souza, Helivaldo D.S.,De Sousa, Roxana P.F.,Lira, Bruno F.,Vilela, Raquel F.,Borges, Nathalie H.P.B.,De Siqueira?Junior, José P.,Lima, Edeltrudes O.,Jardim, Jeane U.G.,Da Silva, Gracielle A.T.,Barbosa?Filho, José M.,De Athayde?Filho, Petr?nio F.
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p. 188 - 197
(2018/12/13)
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- Combined structure- and ligand-based virtual screening aiding discovery of selenoglycolicamides as potential multitarget agents against Leishmania species
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Leishmaniasis is a neglected disease that does not have adequate treatment. We created a database with 30 selenoglycolicamides and evaluated their potential anti-Leishmanial activity (L. amazonensis and L. donovani) through ligand- and structure-based vir
- de Sousa Luis, José Alixandre,da Silva Souza, Helivaldo Diógenes,Lira, Bruno Freitas,da Silva Alves, Francinara,de Athayde-Filho, Petr?nio Filgueiras,de Souza Lima, Tatjana Keesen,Rocha, Juliana Camara,Mendon?a Junior, Francisco Jaime Bezerra,Scotti, Luciana,Scotti, Marcus Tullius
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- Discovery and optimization of 3,4,5-trimethoxyphenyl substituted triazolylthioacetamides as potent tubulin polymerization inhibitors
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Based on our previous research, three series of new triazolylthioacetamides possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities and inhibition of tubulin polymerization. The most promising compounds 8b and 8j demonstrated more significant antiproliferative activities against MCF-7, HeLa, and HT-29 cell lines than our lead compound 6. Moreover, analogues 8f, 8j, and 8o manifested more potent antiproliferative activities against HeLa cell line with IC50 values of 0.04, 0.05 and 0.16 μM, respectively, representing 100-, 82-, and 25-fold improvements of the activity compared to compound 6. Furthermore, the representative compound, 8j, was found to induce significant cell cycle arrest at the G2/M phase in HeLa cell lines via a concentration-dependent manner. Meanwhile, compound 8b exhibited the most potent tubulin polymerization inhibitory activity with an IC50 value of 5.9 μM, which was almost as active as that of CA-4 (IC50 = 4.2 μM). Additionally, molecular docking analysis suggested that 8b formed stable interactions in the colchicine-binding site of tubulin.
- Yang, Fang,He, Cai-Ping,Diao, Peng-Cheng,Hong, Kwon Ho,Rao, Jin-Jun,Zhao, Pei-Liang
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- Pharmacological and physicochemical profile of arylacetamides as tools against human cancers
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Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations.
- Ferreira, Paulo Michel Pinheiro,Machado, Kátia da Concei??o,Lavorato, Stefania Neiva,de Oliveira, Fátima de Cássia Evangelista,Silva, Jurandy do Nascimento,de Almeida, Antonia Amanda Cardoso,Santos, Luciano de Souza,Silva, Valdenizia Rodrigues,Bezerra, Daniel Pereira,Soares, Milena Botelho Pereira,Pessoa, Cláudia,de Moraes Filho, Manoel Odorico,Ferreira, José Roberto de Oliveira,Sousa, Jo?o Marcelo de Castro e,Maltarollo, Vinícius Gon?alves,Alves, Ricardo José
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- Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains
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Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of human immunodeficiency virus (HIV) infection. These regimens are extremely effective in suppressing virus replication. Recently, our research group identified some N1-aryl-2-arylthioacetamido-benzimidazoles as a novel class of NNRTIs. In this research work we report the design, the synthesis and the structure–activity relationship studies of new compounds (20–34) in which some structural modifications have been introduced in order to investigate their effects on reverse transcriptase (RT) inhibition and to better define the features needed to increase the antiviral activity. Most of the new compounds proved to be highly effective in inhibiting both RT enzyme at nanomolar concentrations and HIV-1 replication in MT4 cells with minimal cytotoxicity. Among them, the most promising N1-aryl-2-arylthioacetamido-benzimidazoles and N1-aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K. The best results were observed for derivatives 29 and 33 active also against the double mutants F227L and V106A. Computational approaches were applied in order to rationalize the potency of the new synthesized inhibitors.
- Monforte, Anna Maria,De Luca, Laura,Buemi, Maria Rosa,Agharbaoui, Fatima E.,Pannecouque, Christophe,Ferro, Stefania
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p. 661 - 674
(2018/01/03)
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- Synthesis, antiproliferative evaluation, and structure–activity relationships of novel triazole–isoindoline hybrids bearing 3,4,5-trimethoxyphenyl moiety
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As an aspect of our ongoing research on developing novel antiproliferative agents, 31 new triazole–isoindoline hybrids bearing 3,4,5-trimethoxyphenyl moiety were synthesized and evaluated for their antiproliferative activity against four cancer cell lines (HepG2, HeLa, PC-3, and HCT116). Some compounds showed excellent potency, and compared to fluorouracil, the most promising compound 6s exhibited 5.8-, 4.3-, and 1.3- fold increase in activities against HeLa, HepG2, and PC-3 cell lines with IC50 values of 9.7, 10.7, and 16.8?μM, respectively. Moreover, structure–activity relationship studies indicated that a much shorter amide linkage and electron-withdrawing groups at phenyl ring of the acetamide fragment contribute to the antitumour activity.
- Li, Qiu,Chen, Peng,Yang, Haikui,Luo, Miaolan,You, Wenwei,Zhao, Peiliang
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p. 651 - 659
(2018/02/28)
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- 1,3-dimethyl-7-substituted-quinazolinyl-2,4-diones, and synthesis method and application thereof
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The invention discloses 1,3-dimethyl-7-substituted-quinazolinyl-2,4-diones. The structural general formula of the compounds is disclosed in the specification, wherein R1 is hydrogen or ethyl; and R2 is a benzene ring, benzene ring derivative, heterocyclic ring or aliphatic hydrocarbon. Part of compounds have favorable inhibiting activities for Candida albicans, Aspergillus flavus, Torula histolytica and Aspergillus fumigatus. The compounds have obvious inhibiting activities for chitin synthetase, have favorable antibacterial effects, and can be used for preparing drugs for anti-pathogenic microorganisms.
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Paragraph 0056; 0057; 0058; 0059; 0060; 0071; 0072
(2017/07/31)
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- Synthesis, in?vitro evaluation and molecular docking studies of novel triazine-triazole derivatives as potential α-glucosidase inhibitors
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A novel series of triazine-triazole derivatives 7a–7m were synthesized, characterized by1H NMR and evaluated for their α-glucosidase inhibitory activity. All the synthesized compounds displayed potent α-glucosidase inhibitory activity with IC50range of 11.63?±?0.15 to 37.44?±?0.35?μM, when compared to the standard drug acarbose (IC50?=?817.38?±?6.27?μM). Among the series, compound 7i (IC50?=?11.63?±?0.15?μM) bearing 2,5-dichloro substitution at phenyl ring, represented the most potent α-glucosidase inhibitory activity. Molecular docking studies of the most active compounds with the homology modelled α-glucosidase were also performed to explore the possible inhibitory mechanism. Our studies shown that these triazine-triazole derivatives are a new class of α-glucosidase inhibitors.
- Wang, Guangcheng,Peng, Zhiyun,Wang, Jing,Li, Xin,Li, Juan
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p. 423 - 429
(2016/10/03)
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- Synthesis, molecular docking and α-glucosidase inhibition of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides
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A novel series of 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-N-arylacetamides 5a–5q have been synthesized and evaluated for their α-glucosidase inhibitory activity. All newly synthesized compounds exhibited potent α-glucosidase inhibitory activity in the range of IC50?=?12.46?±?0.13–72.68?±?0.20?μM, when compared to the standard drug acarbose (IC50?=?817.38?±?6.27?μM). Among the series, compound 5j (12.46?±?0.13?μM) with strong electron-withdrawing nitro group on the arylacetamide moiety was identified as the most potent inhibitor of α-glucosidase. Molecular docking study was carried out to explore the binding interactions of these compounds with α-glucosidase. Our study identifies a novel series of potent α-glucosidase inhibitors for further investigation.
- Wang, Guangcheng,Li, Xin,Wang, Jing,Xie, Zhenzhen,Li, Luyao,Chen, Ming,Chen, Shan,Peng, Yaping
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p. 1115 - 1118
(2017/06/19)
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- Synthesis and antiviral evaluation of novel N-6 substituted adenosine analogues
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A series of adenosine analogues were synthesized and their biological evaluation was tested against Coxsackie virus B3 (CVB3) and Herpes simplex virus type 1(HSV-1) in HEp-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were calculated. Analogues with piperazine derivatives 8b showed promising activities against CVB3 with a lower IC50value and higher selectivity index, their efficacy was better than that of the commercialized medicine, Ribavirin. These described adenosine analogues exhibit potent antiviral activities against several viruses, and offer new leads for further development.
- Hao, Youwu,Zhou, Gaohui,Wu, Wei,Zhang, Yang,Tao, Liming,Yao, Jianhua,Xu, Wenping
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p. 190 - 193
(2016/12/27)
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- Synthesis and cytotoxic evaluation of some 2-{4-[(2-oxo-1,2-dihydro-3h-indol-3-ylidene)methyl] phenoxy}-n-phenylacetamide
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A series of 2-oxindole derivatives were synthesized and evaluated for cytotoxic activity against different human and murine cancer cell lines and cancer chemopreventive activity. Among the tested compounds VS-06, 08, 12 and 17 displayed cytotoxic activity in the range of 5.0 to 8.5 μM against human T-lymphocyte cells (CEM). Results showed that molecules with electron withdrawing substituent at 4 position of N-phenylacetamide group exhibited an increase in activity against the human tumor cell line CEM. The cancer chemopreventive effect of VS-01 (IC50 = 451 nM) displayed equipotent activity in comparison to standard oleanolic acid (IC50 = 449 nM).
- Bhadauria, Vivek Singh,Sravanthi, Vishnu,Kumar, Sujeet,Das, Debajyoti,De Clercq, Erik,Schols, Dominique,Tokuda, Harukuni,Karki, Subhas S.
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p. 137 - 145
(2017/01/17)
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- Carbamylmethyl Mercaptoacetate Thioether: A Novel Scaffold for the Development of L1 Metallo-β-lactamase Inhibitors
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Given the clinical importance of metallo-β-lactamases (MβLs), a new scaffold, N-substituted carbamylmethyl mercaptoacetate thioether, was constructed. The obtained molecules 1-16 inhibited MβLs from all three subclasses, but preferentially L1 from subclass B3. Compound 9 with a p-carboxyphenyl substituent exhibited the broadest spectrum with at least 70% inhibition of enzymes from all subclasses at 100 μM, while compound 5 with a p-methylphenyl substituent was the most potent inhibitor of any individual enzyme, with 97% inhibition at 100 μM and an IC50 value of 0.41 μM against L1. Isothermal titration calorimetry assays corroborate findings from UV-vis spectrophotometric assays that the inhibition of L1 by 5 is dose-dependent. Docking studies suggest that the carboxyl group, the sulfide atom, and the carbonyl group of the carbamyl coordinate Zn2 in a chelating fashion. Using E. coli cells expressing L1, 6 and 8 were able to decrease cefazolin minimum inhibitory concentration 8-fold.
- Chang, Ya-Nan,Xiang, Yang,Zhang, Yue-Juan,Wang, Wen-Ming,Chen, Cheng,Oelschlaeger, Peter,Yang, Ke-Wu
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supporting information
p. 527 - 532
(2017/05/19)
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- Side chain-functionalized aniline-derived ursolic acid derivatives as multidrug resistance reversers that block the nuclear factor-kappa B (NF-κB) pathway and cell proliferation
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A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing functionalized aniline or amide side chains were synthesized and evaluated for inhibition of NF-κB as well as their antitumor effects. These compounds exhibited significant inhibition activity toward NF-κB with IC50 values at micromolar concentrations in the NCI-H460 lung adenocarcinoma cell line. A docking study of the most active compound 5Y8 revealed key interactions between 5Y8 and the active site of NF-κB in which the functionalized amide moiety at the C-28 position and an ester group at the C-3 position were important for improving the activity. In particular, compound 5Y8 appeared to be the most potent compound against the NCI-H460 cell line, and displayed similar efficiency in drug-sensitive versus drug-resistant cancer cell lines, at least partly, by blocking the NF-κB signaling pathway and inducing apoptosis. Mechanistically, compound 5Y8 might trigger the apoptotic signaling pathway. Thus, the rational design of UA derivatives with functionalized aniline or amide side chains offers significant potential for the discovery of a new class of NF-κB inhibitors with the ability to induce apoptosis and reverse multidrug resistance in the NCI-H460 lung adenocarcinoma cell line.
- Huang, Ri-Zhen,Hua, Shi-Xian,Liao, Zhi-Xin,Huang, Xiao-Chao,Wang, Heng-Shan
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p. 1421 - 1434
(2017/07/25)
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- Pyrrolizines: Design, synthesis, anticancer evaluation and investigation of the potential mechanism of action
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A novel set of pyrrolizine-5-carboxamides has been synthesized and evaluated for their anticancer potential against human breast MCF-7, lung carcinoma A549 and hepatoma Hep3B cancer cell lines. Compound 10c was the most active against MCF-7 with IC50
- Gouda, Ahmed M.,Abdelazeem, Ahmed H.,Omar, Hany A.,Abdalla, Ashraf N.,Abourehab, Mohammed A.S.,Ali, Hamed I.
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p. 5637 - 5651
(2017/10/09)
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- Synthesis and biological evaluation of potential inhibitors of the cysteine proteases cruzain and rhodesain designed by molecular simplification
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Analogues of 8-chloro-N-(3-morpholinopropyl)-5H-pyrimido[5,4-b]indol-4-amine 1, a known cruzain inhibitor, were synthesized using a molecular simplification strategy. Five series of analogues were obtained: indole, pyrimidine, quinoline, aniline and pyrrole derivatives. The activity of the compounds was evaluated against the enzymes cruzain and rhodesain as well as against Trypanosoma cruzi amastigote and trypomastigote forms. The 4-aminoquinoline derivatives showed promising activity against both enzymes, with IC50values ranging from 15 to 125?μM. These derivatives were selective inhibitors for the parasitic proteases, being unable to inhibit mammalian cathepsins B and S. The most active compound against cruzain (compound 5a; IC50?=?15?μM) is considerably more synthetically accessible than 1, while retaining its ligand efficiency. As observed for the original lead, compound 5a was shown to be a competitive enzyme inhibitor. In addition, it was also active against T. cruzi (IC50?=?67.7?μM). Interestingly, the pyrimidine derivative 4b, although inactive in enzymatic assays, was highly active against T. cruzi (IC50?=?3.1?μM) with remarkable selectivity index (SI?=?128) compared to uninfected fibroblasts. Both 5a and 4b exhibit drug-like physicochemical properties and are predicted to have a favorable ADME profile, therefore having great potential as candidates for lead optimization in the search for new drugs to treat Chagas disease.
- Braga, Saulo Fehelberg Pinto,Martins, Luan Carvalho,da Silva, Elany Barbosa,Sales Júnior, Policarpo Ademar,Murta, Silvane Maria Fonseca,Romanha, Alvaro José,Soh, Wai Tuck,Brandstetter, Hans,Ferreira, Rafaela Salgado,de Oliveira, Renata Barbosa
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supporting information
p. 1889 - 1900
(2017/03/08)
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- Rational design and synthesis of dihydropyrimidine based dual binding site acetylcholinesterase inhibitors
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Based on the pharmacological importance of dihydropyrimidine (DHPM) scaffold, substituted DHPMs linked with acetamide linker to substituted aromatic anilines were synthesized and evaluated for their potency as acetylcholinesterase (AChE) and butyrylcholin
- Ahmad, Sufyan,Iftikhar, Fatima,Ullah, Farhat,Sadiq, Abdul,Rashid, Umer
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- 1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: Synthesis and in vitro biological evaluation
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In our endeavor towards the development of effective VEGFR-2 inhibitors, three novel series of phthalazine derivatives based on 1-piperazinyl-4-arylphthalazine scaffold were synthesized. All the newly prepared phthalazines 16a-k, 18a-e and 21a-g were evaluated in vitro for their inhibitory activity against VEGFR-2. In particular, compounds 16k and 21d potently inhibited VEGFR-2 at sub-micromolar IC50 values 0.35 ± 0.03 and 0.40 ± 0.04 μM, respectively. Moreover, seventeen selected compounds 16c-e, 16g, 16h, 16j, 16k, 18c-e and 21a-g were evaluated for their in vitro anticancer activity according to US-NCI protocol, where compounds 16k and 21d proved to be the most potent anticancer agents. While, compound 16k exhibited potent broad spectrum anticancer activity with full panel GI50 (MG-MID) value of 3.62 μM, compound 21d showed high selectivity toward leukemia and prostate cancer subpanels [subpanel GI50 (MG-MID) 3.51 and 5.15 μM, respectively]. Molecular docking of compounds16k and 21d into VEGFR-2 active site was performed to explore their potential binding mode.
- Abou-Seri, Sahar M.,Eldehna, Wagdy M.,Ali, Mamdouh M.,Abou El Ella, Dalal A.
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p. 165 - 179
(2015/11/25)
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- Design, synthesis and biological evaluation of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives
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Based on our previous work, a series of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that some compounds possessed significant antiproliferative activities against four cancer cell lines, HepG2, HCT116, PC-3, and Hela. Particularly, the most promising compound 8d displayed 184-, 18-, and 17-fold improvement compared to fluorouracil in inhibiting HCT116, Hela and PC-3 cell proliferation with IC50values of 0.37, 2.94, and 31.31 μM, respectively. Most interestingly, the compound did not affect the normal human embryonic kidney cells, HEK-293. Moreover, mechanistic investigation showed that the representative compound 8d induced apoptosis and blocked cell cycle in G2/M phase in Hela cells in a dose-dependent manner. These findings suggest that compound 8d may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
- Zhao, Pei-Liang,Chen, Peng,Li, Qiu,Hu, Meng-Jin,Diao, Peng-Cheng,Pan, En-Shan,You, Wen-Wei
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p. 3679 - 3683
(2016/07/21)
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- Synthesis and anti-leishmanial evaluation of 1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline derivatives against Leishmania infantum
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In the present study, antileishmanial activity of sixteen novel series of tetrahydro-β-carboline derivatives against transgenic infrared fluorescent Leishmania infantum strain has been reported. Among these reported analogues, most of the compounds exhibited potent inhibition against both promastigote (IC50from 1.99?±?1.40 to 20.69?±?0.95?μM) and amastigote (IC50from 0.67?±?0.05 to 4.16?±?0.008?μM) forms of L.?infantum. Moreover, compound 7l, displayed most potent and selective inhibition of parasite amastigote form with IC500.67?±?0.05?μM, selectivity index >298.5 and was comparable with standard drug amphotericin B. From this study, a new class of tetrahydro-β-carboline derivatives with potent antileishmanial activity was identified and it needs further extensive study to optimize the lead molecules to win the battle against severe and neglected disease leishmaniasis.
- Ashok, Penta,Chander, Subhash,Tejería, Ana,García-Calvo, Laura,Bala?a-Fouce, Rafael,Murugesan, Sankaranarayanan
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p. 814 - 821
(2016/08/23)
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- Synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives incorporating benzisoselenazolone scaffold as potential antitumor agents
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Background: Based on the biological signi-cance of benzisoselenazolone and 1,3,4-thiadiazole, a series of novel 1,3,4-thiadiazole derivatives incorporating benzisoselenazolone scaffold were designed and synthesized with ebselen as a lead compound. Methods: Meanwhile, their in vitro antitumor activities were evaluated against SMMC-7721, MCF-7 and A549 human cancer cell lines by CCK-8 assay. Results: The preliminary bioassay results demonstrated that all tested compounds 4a-q showed potent antitumor activities, and some compounds exhibited better effects than positive control ethaselen and 5-fluorouracil (5-FU) against various cancer cell lines. Furthermore, compounds 4b and 4m showed significant antitumor activities against SMMC-7721 cells with IC50 values of 1.89 and 1.89 μM, respectively. Compounds 4c and 4n displayed highly effective biological activities against MCF-7 cells with IC50 values of 2.88 and 2.28 μM, respectively. Compound 4i showed the best inhibitory effect against A549 cells with IC50 value of 1.76 μM. Conclusion: The pharmacological results suggest that the substituent groups of phenyl ring on the 1,3,4-thiadiazole are vital for modulating antitumor activities against various cancer cell lines.
- Fu, Xiaoyun,Li, Sha,Jing, Fen,Wang, Xuefeng,Li, Baolin,Zhao, Jijun,Liu, Yuming,Chen, Baoquan
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p. 631 - 639
(2016/10/18)
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- Synthesis and antifungal activity against candida strains of mesoionic system derived from 1,3-Thyazolium-5-Thiolate
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A series of ten new compounds have been synthetized in satisfactory yields (85-95percent) through the treatment of isopropyl mesoionic 1,3-Thiazolium-5-Thiolate with 2-chloro-N-Arylacetamides and characterized by elemental analysis, infrared (IR), 1H and
- Peixoto, Isabelle N.,Souza, Helivaldo D. S.,Lira, Bruno F.,Silva, Daniele F.,Lima, Edeltrudes O.,Barbosa-Filho, José M.,De Athayde-Filho, Petr?nio F.
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p. 1807 - 1813
(2016/10/18)
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- Synthesis of new donepezil analogues and investigation of their effects on cholinesterase enzymes
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Donepezil (DNP), an acetylcholinesterase (AChE) inhibitor, is one of the most preferred choices in Alzheimer diseases (AD) therapy. In the present study, 38 new DNP analogues were synthesized. Structures of the synthesized compounds (1–38) were elucidated by IR,1H NMR,13C NMR and HRMS spectroscopic methods and elemental analysis. Inhibitory potential of the compounds on cholinesterase enzymes was investigated. None of the compounds displayed significant activity on butyrylcholinesterase (BChE) enzyme. On the other hand, compounds 26–29 indicated important inhibitory activity on AChE enzyme. Kinetic studies were performed in order to observe the effects of the most active compounds on substrate-enzyme relationship. Cytotoxicity studies and theoretical calculation of pharmacokinetic properties were also carried out to get an information about toxicity and pharmacokinetic profiles of the compounds. The compounds 26–29 were found to be nontoxic at their effective concentrations against AChE. A good pharmacokinetic profile was predicted for these compounds. Docking studies were performed for the most active compounds 26–29 and interaction modes with enzyme active sites were determined. Docking studies revealed that there is a strong interaction between the active sites of AChE enzyme and analyzed compounds.
- Sa?l?k, Begüm Nurpelin,Ilg?n, Sinem,?zkay, Yusuf
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p. 1026 - 1040
(2016/11/09)
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- Sulfonamide-1,3,5-triazine-thiazoles: Discovery of a novel class of antidiabetic agents: Via inhibition of DPP-4
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Dipeptidyl peptidase-4 (DPP-4) inhibitors are a novel class of antidiabetic drugs used for treating type 2 diabetes mellitus. In the present study, a novel hybrid sulphonamide-1,3,5-triazine-thiazole derivatives were synthesized and characterized by 1H-NMR, 13C-NMR, FT-IR, mass spectroscopy and elemental analysis. The result showed that among the tested compounds, 8c was found to be a more potent inhibitor of DPP-4 (2.32 nM) than the alogliptin standard. Moreover, molecular docking results showed that ligand 8c was efficiently docked into the active site of the catalytic triad of Ser630, Asp708 and His740, encompassing both the S1 and S2 pocket with a CDOCKER interaction energy of 57.80. The in vitro results were further substantiated by in vivo blood glucose lowering effects in experimental subjects. The results of the investigation showed that compound 8c exhibited concentration-dependent improvement of glucose tolerance in ICR after oral administration. It has been also found that compound 8c (30 mg kg-1) showed a reduction in the area under the curve from 0 to 120 min [(AUC) 0-120 min] to 37.46%, which was found to be approximately similar to the hypoglycemic profile of alogliptin (standard). The activity of compound 8c was also investigated in STZ-induced diabetic rats where it showed a dose-dependent decrease in blood glucose levels together with an improvement in insulin levels probably via inhibition of DPP-4. The effect of compound 8c was also investigated on the lipid profile and antioxidant enzyme system.
- Gao, Hai-De,Liu, Peng,Yang, Yang,Gao, Fang
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p. 83438 - 83447
(2016/11/09)
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- Synthesis and antimicrobial activities of various N-phenyl-2-{[5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides
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A new series of various N-phenyl-2-{[5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamidehave been synthesized by the condensation of 5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole-2-thiol and 2-chloro-N-(aryl)-acetamides. The novel compound structures have been established on the basis of their substituted N-chloro aryl acetamide derivatives. All the compounds have been characterized by FT-IR, mass spectra, 1H and 13C NMR spectroscopy. These new compounds have been evaluated for their in vitro antibacterial and anti-fungal activities.
- Shukla, Maharshi B.,Mahyavanshi, Jyotindra B.,Parmar, Kokila A.
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p. 374 - 380
(2017/01/18)
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- Discovery of novel AHLs as potent antiproliferative agents
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Three series of novel AHL analogs were synthesized and evaluated for their in vitro cytotoxic activity against four human cancer cell lines. The SARs investigation indicated that AHLs with a terminal phenyl group, especially those with the chalcone scaffold had remarkably enhanced cytotoxicity than those with the hydrophobic side chains. Besides, some of these compounds were much more potent than 5-Fu and natural OdDHL. Through the detailed SARs discussions, we found that compounds 10a-k and 14 with the 4-amino chalcone scaffold showed excellent inhibition against all the tested cancer cell lines and were much more potent than 5-Fu and AHLs. Such scaffold may act as a template for further lead optimization. Compound 10i with a 3, 4, 5-trimethoxy group was the most potent one against all the tested cancer cell lines. Flow cytometry analysis indicated that analog 11e induced the cellular apoptosis and cell cycle arrest of MCF-7 cells at G2/M phase in a concentration-and time-dependent manner.
- Ren, Jing-Li,Zhang, Xu-Yao,Yu, Bin,Wang, Xi-Xin,Shao, Kun-Peng,Zhu, Xiao-Ge,Liu, Hong-Min
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p. 321 - 329
(2015/03/04)
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- Synthesis and in vitro kinetic study of novel mono-pyridinium oximes as reactivators of organophosphorus (OP) inhibited human acetylcholinesterase (hAChE)
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A series of mono pyridinium oximes linked with arenylacetamides as side chains were synthesized and their in vitro reactivation potential was evaluated against human acetylcholinesterase (hAChE) inhibited by organophosphorus inhibitors (OP) such as sarin, VX and tabun. The reactivation data of the synthesized compounds were compared with those obtained with standard reactivators such as 2-PAM and obidoxime. The dissociation constant (KD) and specific reactivity (kr) of the oximes were also determined by performing reactivation kinetics against OP inhibited hAChE. Among the synthesized compounds, oximes 1-(2-(4-cyanophenylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (12a) and 4-((hydroxyimino)methyl)-1-(2-(4-methoxyphenylamino)-2-oxoethyl)pyridinium chloride (2a) were found most potent reactivators for hAChE inhibited by sarin. In case of VX inhibited hAChE majority of the oximes have shown good reactivation efficacies. Among these oximes 1-(2-(benzylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (18a), 4-((hydroxyimino)methyl)-1-(2-(4-(methoxycarbonyl)phenylamino)-2-oxoethyl)pyridinium-chloride (14a) and 12a were found to surpass the reactivation potential of 2-PAM and obidoxime. However, the synthesized oximes showed marginal reactivation efficacies in case of tabun inhibited hAChE. The pKa value of the oximes were determined and correlated with their observed reactivation potential.
- Valiveti, Aditya Kapil,Bhalerao, Uma M.,Acharya, Jyotiranjan,Karade, Hitendra N.,Gundapu, Raviraju,Halve, Anand K.,Kaushik, Mahabir Parshad
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p. 125 - 132
(2015/06/25)
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- Chloroquinoline-acetamide hybrids: A promising series of potential antiprotozoal agents
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In an endeavour to develop efficacious antiprotozoal agents 2-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]acetamide derivatives were synthesized and screened in vitro against the HM1:IMSS strain of E. histolytica and 3D7 strain of P. falciparum. Among the twenty-seven synthesized compounds, eleven evinced propitious anti-amoebic activity with IC50 values ranging from 0.41 to 1.80 μM) lower than the standard drug metronidazole (IC50 1.80 μM). All the compounds inhibited the in vitro growth of P. falciparum (IC50 range: 0.30-33.52 μM). Compounds A22 and A25 were found to be the most active antimalarial derivatives, and compound A16 the most active in inhibiting β-haematin formation; however compound A25 displayed the more favourable safety profile. The crystal structure for the compounds A7, A8, A12 and A21 was also determined. The molecular docking of crystal resolved inhibitors with PfDHFR allowed identification of stabilizing interactions within enzyme active sites. These compounds affirm the potential for further derivatives to enhance antiprotozoal activity whilst retaining their safety profile.
- Inam, Afreen,Van Zyl, Robyn L.,Van Vuuren, Natasha J.,Chen, Chien-Teng,Avecilla, Fernando,Agarwal, Subhash M.,Azam, Amir
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p. 48368 - 48381
(2015/06/16)
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- Facile synthesis and antifungal activity of dithiocarbamate derivatives bearing an amide moiety
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Two series of novel dithiocarbamate derivatives bearing an amide moiety, 3a-i and 4a-i, were synthesized by a facile method, and the structures of the derivatives were confirmed by elemental analysis and 1H-NMR, 13C- -NMR and high-resolution mass spectrometry (HRMS). Their antifungal activity against five phytopathogenic fungi were evaluated, and the results showed that most of the target compounds displayed low antifungal activity in vitro against Gibberella zeae, Cytospora sp., Colletotrichum gloeosporioides, Alternaria solani, and Fusarium solani at a concentration of 100 mg L-1. However, two compounds, 4f and 4g, exhibited significant activity against A. solani and C. gloeosporioides, respectively.
- Li, Yu-Wen,Li, Shu-Tao
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p. 1367 - 1374
(2016/02/18)
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- 6-bromo-2,3-dioxoindolin phenylacetamide derivatives: Synthesis, potent CDC25B, PTP1B inhibitors and anticancer activity
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A series of 6-bromo-2,3-dioxoindolin phenylacetamide derivatives was synthesized and evaluated for inhibitory activity against CDC25B and PTP1B. Most of the synthesized compounds showed potential inhibitory activities for CDC25B and PTP1B with compound 12 being the most potent (IC50=3.87μmol/L and 2.98 μmol/L, respectively). Compound 12 also exhibited higher cytotoxic activity against three cancer cell lines (HeLa, A549 and HCT116). In addition, compound 12 delayed the potent tumor inhibitory activity in a colo205 xenograft model in vivo.
- Zhao, Shui-Lian,Peng, Zhou,Zhen, Xing-Hua,Han, Yan,Jiang, Hai-Ying,Qu, You-Le,Guan, Li-Ping
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p. 529 - 536
(2016/03/22)
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- Discovery of novel type II c-Met inhibitors based on BMS-777607
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Twenty-two new analogs based on the structure of BMS-777607 were designed, synthesized, and evaluated to determine their biological activities. Compounds bearing a cyclic sulfonamide or α-chloropiperidone scaffold exhibited good activity, which may provid
- Zhang, Wei,Ai, Jing,Shi, Dakuo,Peng, Xia,Ji, Yinchun,Liu, Jian,Geng, Meiyu,Li, Yingxia
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p. 254 - 266
(2014/05/20)
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- Synthesis, cytotoxic study and docking based multidrug resistance modulator potential analysis of 2-(9-oxoacridin-10(9H)-yl)-N-phenyl acetamides
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The present study describes the synthesis of fifteen 2-(9-oxoacridin-10(9H) -yl)-N-phenyl acetamide derivatives (13a-o) through condensation of 2-chloro-N-phenyl acetamides (12a-o) with acridone molecule (10). All the synthesized compounds were screened f
- Kumar, Rajesh,Kaur, Maninder,Bahia, Malkeet Singh,Silakari, Om
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- MRI ParaCEST agents that improve amide based pH measurements by limiting inner sphere water T2 exchange
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A series of Dy3+ and Tm3+ tetra-substituted DOTAM paraCEST agents incorporating para-substituted anilines has been synthesized and their paraCEST and relaxation properties evaluated. The response of selected agents (aniline and p-met
- Milne, Mark,Lewis, Melissa,McVicar, Nevin,Suchy, Mojmir,Bartha, Robert,Hudson, Robert H. E.
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p. 1666 - 1674
(2014/01/06)
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- Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents
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A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 5l, and 5o had strong inhibitory potency against CHS. Compound 5c, which has the highest potency among these compounds, had a half-inhibition concentration (IC50) of 0.08 mmol/L, while polyoxin B as positive drug had IC50 of 0.18 mmol/L. These IC 50 values of compounds 5i, 5m, 5n, and 5s were greater than 0.75 mmol/L, which revealed that those compounds had weak inhibition activity against CHS. Moreover, most of these compounds exhibited moderate to excellent antifungal activities. In detail, to Candida albicans, the activities of compound 5g and 5k were 8-fold stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to Aspergillus flavus, the activities of 5g, 5l and 5o were16-fold stronger than that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus neoformans, the minimum-inhibition- concentration (MIC) values of compounds 5c, 5d, 5e and 5l were comparable to those of fluconazole and polyoxin B. The antifungal activities of these compounds were positively correlated to their IC50 values against CHS. Furthermore, these compounds had negligible actions to bacteria. Therefore, these compounds were promising selective antifungal agents.
- Ji, Qinggang,Yang, Dan,Wang, Xin,Chen, Chunyan,Deng, Qiao,Ge, Zhiqiang,Yuan, Lvjiang,Yang, Xiaolan,Liao, Fei
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p. 3405 - 3413
(2014/06/23)
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