5782-85-4Relevant academic research and scientific papers
Discovery of Novel Neuraminidase Inhibitors by Structure-Based Virtual Screening, Structural Optimization, and Bioassay
Yu, Rao,Cheng, Li Ping,Li, Meng,Pang, Wan
, p. 1667 - 1673 (2019)
Neuraminidase (NA) is a significant therapeutic target for treating influenza. In this study, a new lead NA inhibitor AN-329/10738021 was discovered by structure-based virtual screening, molecular dynamics simulations, and bioassay validation. Optimization of lead AN-329/10738021, which holds a novel scaffold of N′-benzylidene benzohydrazone, leads to discovery of some novel NA inhibitors Y-1-Y-11. Compound Y-1 exerts the best inhibition activity (IC50 = 0.21 μM) against NA, which is better than oseltamivir carboxylate (OSC) (IC50 = 3.04 μM) and lead AN-329/10738021 (IC50 = 1.92 μM). Molecular docking analysis indicates that the good potency of Y-1 may be ascribed to the elongation of the benzylidene moiety of the molecule to the 430-cavity. The results of this study may offer useful reference for development of novel NA inhibitors.
Synthesis, antiproliferative activity and molecular properties predictions of galloyl derivatives
Da Silva, Marciane Maximo,Comin, Marina,Duarte, Thiago Santos,Foglio, Mary Ann,De Carvalho, Jo?o Ernesto,Do Carmo Vieira, Maria,Formagio, Anelise Samara Nazari
, p. 5360 - 5373 (2015)
The present study was designed to investigate the in vitro antiproliferative activity against ten human cancer cell lines of a series of galloyl derivatives bearing substituted-1,3,4-oxadiazole and carbohydrazide moieties. The compounds were also assessed in an in silico study of the absorption, distribution, metabolism and excretion (ADME) in the human body using Lipinski's parameters, the topological polar surface area (TPSA) and percentage of absorption (%ABS). In general, the introduction of N'-(substituted)-arylidene galloyl hydrazides 4-8 showed a moderate antitumor activity, while the 2-methylthio- and 2-thioxo-1,3,4-oxadiazol-5-yl derivatives 9 and 10 led to increased inhibition of cancer cell proliferation. The precursor compound methyl gallate 2 and the intermediary galloyl hydrazide 3 showed greater antiproliferative activity with GI50 values 50 = 0.05-5.98 μM) was also shown, with compounds 2, 3, 9 and 10 with GI50 ≤ 0.89 μM standing out in this respect. The in silico study revealed that the compounds showed good intestinal absorption.
Development of gallic acid formazans as novel enoyl acyl carrier protein reductase inhibitors for the treatment of tuberculosis
Saharan, Vanita D.,Mahajan, Supriya S.
, p. 808 - 815 (2017)
The enoyl acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis (MTB) is an attractive target for developing novel antitubercular agents. A series of gallic acid formazans, were computationally designed and docked into the active site of InhA to understand their binding mode and potential to inhibit InhA. Nine compounds from the designed series were identified as potential InhA inhibitors, on the basis of good Glide score. These compounds were synthesized in the laboratory and evaluated for in vitro antitubercular activity against drug-sensitive and multi-drug resistant strains of MTB. Out of nine compounds, three compounds exhibited the most promising MIC of 2?μM against the sensitive strain of MTB, H37Rv. The compounds were evaluated against five resistant strains of MTB. Most of the compounds exhibited activity superior to the standard, linezolid, against all these resistant strains. The mechanism of action of these compounds was concluded to be InhA inhibition, through InhA enzyme inhibition study. Insignificant cytotoxicity of these compounds was observed on RAW 264.7 cell line. Inactivity of all these compounds against gram positive and gram negative bacteria indicated their specificity against MTB. The compounds were further analyzed for ADME properties and showed potential as good oral drug candidates. The results clearly identified some novel, selective and specific InhA inhibitors against sensitive and resistant strains of MTB.
Anti-tyrosinase, antioxidant and antibacterial activities of gallic acid-benzylidenehydrazine hybrids and their application in preservation of fresh-cut apples and shrimps
Peng, Zhiyun,Li, Yufeng,Tan, Lijun,Chen, Lu,Shi, Qiandai,Zeng, Qiao-Hui,Liu, Haiquan,Wang, Jing Jing,Zhao, Yong
, (2022/01/19)
A series of gallic acid-benzylidenehydrazine hybrids were synthesized and evaluated for their tyrosinase inhibitory activity. Thereinto, compounds 5d and 5f potently inhibited tyrosinase with IC50 of 15.3 and 3.3 μM, compared to kojic acid (44.4 μM). The inhibition mechanism suggested that 5d and 5f not only chelated with Cu2+, but also reduced Cu2+ to Cu1+ in the tyrosinase active site. Additionally, 5d and 5f exhibited strong DPPH scavenging and antibacterial activities against Vibrio parahaemolyticu and Staphylococcus aureus, which can be attributed to the function of gallic acid and hydrazone moiety. These compounds also exhibited capacity to preserve fresh-cut apples and shrimps. Finally, 5d and 5f exhibited low cytotoxic activity in a human cell line (HEK293). Therefore, these compounds possess anti-tyrosinase, antioxidant, and antibacterial activities, and can be used in the development of novel food preservatives.
Green synthesis of benzamide-dioxoisoindoline derivatives and assessment of their radical scavenging activity – Experimental and theoretical approach
Bogdanovi?, Goran A.,Milovanovi?, Vesna M.,Novakovi?, Sla?ana,Petrovi?, Vladimir P.,Petrovi?, Zorica D.,Simijonovi?, Du?ica
, (2020/08/19)
A series of benzamide-dioxoisoindoline derivatives 3 was obtained, starting from phthalic anhydride and different benzoyl hydrazides 2, by ultrasound irradiation in water as solvent and without any catalyst. Five obtained compounds have been reported in this study for the first time and crystal structure of compound 3h was determined. All compounds were subjected to experimental determination of their antioxidative potential. DPPH test revealed that newly synthesized phenolic compounds 3d, 3e, and 3j are the best antioxidants. Additionally, probable radical scavenging pathway was analysed for reactions of the most active compounds and some radicals that can be found in living cells.
Amide-imine conjugate involving gallic acid and naphthalene for nano-molar detection, enrichment and cancer cell imaging of La3+: Studies on the catalytic activity of the La3+complex
Shaikh, Ahad,Ghosh, Milan,Mukherjee, Pallabi,Ghosh, Avijit,Molla, Rostam Ali,Ta, Sabyasachi,Das, Debasis
, p. 13501 - 13506 (2020/08/28)
A single crystal X-ray structurally characterized amide-imine conjugate (GAN) derived from gallic acid and naphthalene selectively recognizes La3+ ions via TURN ON fluorescence through ESIPT and CHEF mechanisms. GAN can detect as low as 23.93 × 10-9 M La3+ ions and image intracellular La3+ ions in live HeLa and SiHa cells under a fluorescence microscope in a time- and concentration dependent manner. The corresponding [La(iii)-GAN] complex is established as an efficient catalyst for the synthesis of benzimidazole derivatives from o-phenylenediamine and substituted benzaldehydes. Moreover, GAN is very useful for enrichment of La3+ in ethyl acetate medium. This journal is
Aromatic acyl hydrazone derivative and application thereof as NA inhibitor
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Paragraph 0039; 0044-0046; 0290-0294, (2020/12/30)
The invention relates to an aromatic acyl hydrazone derivative as shown in a structural formula I, pharmaceutically acceptable salt and a pharmaceutical composition thereof, and application of the aromatic acyl hydrazone derivative and the pharmaceutically acceptable salt and the pharmaceutical composition in preparation of an influenza virus neuraminidase inhibitor, wherein R is one of trifluoromethyl, nitryl, 3-methyl-4-nitryl, 3-hydroxyl-4-nitryl, 3-nitryl-4-hydroxyl, hydroxyl, dihydroxyl, dinitryl, 3-methoxy-4-hydroxyl or trihydroxyl; Y is selected from hydroxyl, dihydroxyl, 2-hydroxyl-3-methoxy, 2-hydroxyl-4-methoxy,2-hydroxyl-5-methoxy,2-hydroxyl-6-methoxy,3-hydroxyl-2-methoxy,3-hydroxyl-4-methoxy,3-hydroxyl-5-methoxy,3-hydroxyl-6-methoxy,4-hydroxyl-2-methoxy,4-hydroxyl-3-methoxy,4-hydroxyl-3,5-dimethoxy, trihydroxyl, 4-hydroxyl-3-ethoxy, or 4-hydroxyl-3,5-dimethoxy; w is selected from CH or N; and z is selected from CH or N.
COMPOSITIONS AND METHODS FOR INHIBITING GROUP II INTRON RNA
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Page/Page column 112, (2019/08/12)
The present invention provides compositions and methods for inhibiting group II intron splicing for treating or preventing a disease or disorder associated with an organism harboring an active group II intron. The present invention also provides compositi
Phenolic compounds containing benzyloxy phenyl and preparation method and application of phenolic compounds
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Paragraph 0065; 0066; 0067; 0068, (2017/09/19)
The invention discloses phenolic compounds (I) containing benzyloxy phenyl and a preparation method and application of the phenolic compounds. Pharmacological experiments prove that the phenolic compounds have high inhibiting activity on sphingosine kinase SphK, and part of the compounds has a certain inhibiting effect on inflammatory bowel disease induced by tumor and DSS. The phenolic compounds and the pharmaceutical preparations thereof can be used for preparing drugs for treating a series of cancer and inflammatory diseases such as colon cancer, lung cancer, breast cancer, liver cancer, stomach cancer, inflammatory bowel disease, hepatitis, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis and multiple sclerosis.
Development of hydroxy-based sphingosine kinase inhibitors and anti-inflammation in dextran sodium sulfate induced colitis in mice
Xi, Meiyang,Ge, Jun,Wang, Xiaojian,Sun, Chenbin,Liu, Tianqi,Fang, Liang,Xiao, Qiong,Yin, Dali
, p. 3218 - 3230 (2016/07/06)
Sphingosine kinase (SphK)-catalyzed production of sphingosine-1-phosphate (S1P) regulates cell growth, survival and proliferation as well as inflammatory status in animals. In recent study we reported the N′-(3-(benzyloxy)benzylidene)-3,4,5-trihydroxybenzohydrazide scaffold as a potent SphK inhibitor. As a continuation of these efforts, 51 derivatives were synthesized and evaluated by SphK1/2 inhibitory activities for structure-activity relationship (SAR) study. Among them, 33 was identified as the most potent SphK inhibitor. Potency of 33 was also observed to efficiently decrease SphK1/2 expression in human colorectal cancer cells (HCT116) and significantly inhibit dextran sodium sulfate (DSS)-induced colitis as well as the decreased expression of interleukin (IL)-6 and cyclooxygenase-2 (COX-2) in mouse models. Collectively, 33 was validated as an effective SphK inhibitor, which can be served as anti-inflammatory agent to probably treat inflammatory bowel diseases in human.
