100377-63-7Relevant articles and documents
Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors
Nisa, Mehr-un,Munawar, Munawar A.,Iqbal, Amber,Ahmed, Asrar,Ashraf, Muhammad,Gardener, Qurra-tul-Ann A.,Khan, Misbahul A.
, p. 396 - 406 (2017)
A novel series of 5-(aroylhydrazinocarbonyl)escitalopram (58–84) have been designed, synthesized and tested for their inhibitory potential against cholinesterases. 3-Chlorobenzoyl- (71) was found to be the most potent compound of this series having IC50 1.80 ± 0.11 μM for acetylcholinesterase (AChE) inhibition. For the butyrylcholinesterase (BChE) inhibition, 2-bromobenzoyl- (76) was the most active compound of the series with IC50 2.11 ± 0.31 μM. Structure-activity relationship illustrated that mild electron donating groups enhanced enzyme inhibition while electron withdrawing groups reduced the inhibition except o-NO2. However, size and position of the substituents affected enzyme inhibitions.. In docking study of AChE, the ligands 71, 72 and 76 showed the scores of 5874, 5756 and 5666 and ACE of ?64.92,-203.25 and ?140.29 kcal/mol, respectively. In case of BChE, ligands 71, 76 and 81 depicted high scores 6016, 6150 and 5994 with ACE values ?170.91, ?256.84 and ?235.97 kcal/mol, respectively.
Molecular docking studies and synthesis of 3, 4-disubstituted triazoles as mycobacterium tuberculosis enoyl-acp reductase and CYP-51 inhibitors
Dasan, Neethu,Babu,George, Shiny
, p. 85 - 91 (2019)
Objective: To design, synthesize and in vitro antitubercular, antifungal and antioxidant evaluation of some novel mercapto 1, 2, 4–triazole derivatives. Methods: New derivatives were designed by using various software like ACD Lab chemsketch, molinspiration and autodock. Designed molecules are obeying Lipinski’s rule of five and having highest binding score was selected for the synthesis. The synthesized compounds were subjected to TLC, melting point determination, FTIR,1H NMR,13C NMR and mass spectral analysis. The newly synthesized compounds were investigated for in vitro antitubercular evaluation by MABA method, antifungal evaluation by cup plate method and antioxidant evaluation by DPPH scavenging assay. Results: A virtual screening was carried out through docking designed compounds into the InhA and CYP-51 binding site to predict if these compounds have an analogous binding mode of the enoyl ACP reductase (InhA) and CYP-51 inhibitors. Three derivatives (4a1, 4a2 and 4a3) were selected for the synthesis with the help of in silico modeling. The selected derivatives were synthesized by a conventional method. All the synthesized compounds showed a characteristic peak in FT IR,1H and13C NMR and mass spectroscopic studies. All the selected derivatives showed antitubercular, antifungal and antioxidant activity. Conclusion: The derivatives were synthesized adopting simple and laboratory friendly reaction conditions to give the target compounds in quantitative yields. Newer derivatives possess good antitubercular, antifungal and antioxidant activity.
Novel arylcarbamate-N-acylhydrazones derivatives as promising BuChE inhibitors: Design, synthesis, molecular modeling and biological evaluation
Yamazaki, Diego A.S.,Rozada, Andrew M.F.,Baréa, Paula,Reis, Elaine C.,Basso, Ernani A.,Sarragiotto, Maria Helena,Seixas, Flávio A.V.,Gauze, Gisele F.
, (2021)
A novel series of arylcarbamate-N-acylhydrazones derivatives have been designed and synthesized as potential anti-cholinesterase agents. In vitro studies revealed that these compounds demonstrated selective for butyrylcholinesterase (BuChE) with potent inhibitory activity. The compounds 10a-d, 12b and 12d were the most potent BuChE inhibitors with IC50 values of 0.07–2.07 μM, highlighting the compound 10c (IC50 = 0.07 μM) which showed inhibitory activity 50 times greater than the reference drug donepezil (IC50 = 3.54 μM). The activity data indicates that the position of the carbamate group in the aromatic ring has a greater influence on the inhibitory activity of the derivatives. The enzyme kinetics studies indicate that the compound 10c has a non-competitive inhibition against BuChE with Ki value of 0.097 mM. Molecular modeling studies corroborated the in vitro inhibitory mode of interaction and show that compound 10c is stabilized into hBuChE by strong hydrogen bond interaction with Tyr128, π-π stacking interaction with Trp82 and CH?O interactions with His438, Gly121 and Glu197. Based on these data, compound 10c was identified as low-cost promising candidate for a drug prototype for AD treatment.
A pH-sensitive near-infrared fluorescent probe with alkaline p: K a for chronic wound monitoring in diabetic mice
Mai, Hengtang,Wang, Yu,Li, Shuang,Jia, Ruizhen,Li, Sixian,Peng, Qian,Xie, Yan,Hu, Xiang,Wu, Song
, p. 7374 - 7377 (2019)
A pH-sensitive near-infrared fluorescent probe with alkaline pKa, AlkaP-1, was developed by incorporating a benzoyl hydrazine group into a cyanine dye. The significant fluorescence changes in the alkaline regions enable the probe to monitor the alkalization process from acute wounds to chronic wounds in diabetic mice.
Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors
Mehr-Un-Nisa,Munawar, Munawar A.,Chattha, Fauzia A.,Kousar, Samina,Munir, Jawaria,Ismail, Tayaba,Ashraf, Muhammad,Khan, Misbahul A.
, p. 6014 - 6024 (2015)
A novel serie of escitalopram triazoles (60-88) and a tetrazole (89) have been synthesized and subjected to a study to establish the inhibitory potential of these compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some selectivity in inhibition has been observed. The 4-chlorophenyl- (75, IC50, 6.71 ± 0.25 μM) and 2-methylphenyl- (70, IC50, 9.52 ± 0.23 μM) escitalopram triazole derivatives depicted high AChE inhibition, while 2-fluorophenyl- (76, IC50 = 4.52 ± 0.17 μM) and 4-fluorophenyl- (78, IC50 = 5.31 ± 0.43 μM) have found to be excellent BChE inhibitors. It has also been observed that ortho, meta and para substituted electron donating groups increase the inhibition, while electron withdrawing groups reduce the inhibition. Docking analyses of inhibitors with AChE have depicted the binding energies for 70 and 75 as ΔGbind -6.42 and -6.93 kcal/mol, respectively, while ligands 76 and 78 have shown the binding affinity ΔGbind -9.04 and -8.51 kcal/mol, respectively, for BChE.
Design, Synthesis and Molecular Docking of Vanillic Acid Derivatives as Amylolytic Enzyme Inhibitors
Gupta, Nishi,Mukerjee, Alok,Mishra, Shanti Bhushan
, p. 427 - 435 (2021)
In the present work, a series of vanillic acid derivatives have been synthesized and tested to exhibit promising amylolytic enzymes inhibition. Structures of the synthesized derivatives were studied by FT-IR, 1H NMR, 13C NMR, EI-MS,
Pyrazole derivatives of medically relevant phenolic acids: Insight into antioxidative and anti-lox activity
Bogdanovi?, Goran A.,Brankovi?, Jovica,Milovanovi?, Vesna,Mladenovi?, Milan,Novakovi?, Sla?ana,Petrovi?, Vladimir P.,Petrovi?, Zorica D.,Simijonovi?, Du?ica
, p. 807 - 819 (2021/10/21)
Background: From the point of view of medicinal chemistry, compounds containing phenolic and pyrazolic moiety are significant since they are often constituents of bioactive compounds. Objective: The aims of this study were to synthesize pyrazole derivatives of medically relevant phenolic acids, confirm their structure, and evaluate their antioxidative and anti-LOX activities. Methods: Phenolic pyrazole derivatives were obtained, starting from esters of medically relevant phenolic acids. The structures of all obtained compounds were determined by NMR and IR spectroscopy, and UV-Vis spectrophotometry. In addition, the single-crystal X-ray diffraction was used. Pyrazole derivatives were tested for their in vitro antioxidative (DPPH assay), and lipoxygenase (LOX) inhibitory ac-tivities. Radical quenching mechanism was estimated using DFT and thermodynamic approach, while molecular docking was used to estimate the binding mode within the enzyme. Results: Pyrazole derivatives were obtained in high yields. The crystal structure of a new compound 3e was determined. Pyrazole derivative with catechol moiety 3d exhibited excellent radical scavenging ac-tivity, while compound 3b exhibited the best anti-LOX activity. Molecular docking study revealed that there is no direct interaction of any ligand with the active site of LOX-Ib, but pyrazoles 3a-e behave as inhibitors blocking the approach of linoleic acid to the active site. Conclusion: In this research, protocatechuic and vanillic acid pyrazole derivatives have been obtained for the first time. In vitro antioxidative assay suggests that pyrazole derivate of protocatechuic acid is a powerful radical scavenger, while anti-LOX assay indicates a pyrazole derivative with 4-hydroxyphenyl moiety.
Aromatic acyl hydrazone derivative and application thereof as NA inhibitor
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Paragraph 0039; 0044-0046; 0274-0278, (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.
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.
Structural design, synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents
Meira, Cássio S.,dos Santos Filho, José Maurício,Sousa, Caroline C.,Anjos, Pamela S.,Cerqueira, Jéssica V.,Dias Neto, Humberto A.,da Silveira, Rafael G.,Russo, Helena M.,Wolfender, Jean-Luc,Queiroz, Emerson F.,Moreira, Diogo R.M.,Soares, Milena B.P.
, p. 1971 - 1985 (2018/03/12)
4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
