842-74-0Relevant academic research and scientific papers
Core-Modified Coelenterazine Luciferin Analogues: Synthesis and Chemiluminescence Properties
Gagnot, Glwadys,Hervin, Vincent,Coutant, Eloi P.,Goyard, Sophie,Jacob, Yves,Rose, Thierry,Hibti, Fatima Ezzahra,Quatela, Alessia,Janin, Yves L.
supporting information, p. 2112 - 2123 (2020/12/18)
In this work on the design and studies of luciferins related to the blue-hued coelenterazine, the synthesis of heterocyclic analogues susceptible to produce a photon, possibly at a different wavelength, is undertaken. Here, the synthesis of O-acetylated derivatives of imidazo[1,2-b]pyridazin-3(5 H)-one, imidazo[2,1-f][1,2,4]triazin-7(1 H)-one, imidazo[1,2-a]pyridin-3-ol, imidazo[1,2-a]quinoxalin-1(5 H)-one, benzo[f]imidazo[1,2-a]quinoxalin-3(11 H)-one, imidazo[1′,2′:1,6]pyrazino[2,3-c]quinolin-3(11 H)-one, and 5,11-dihydro-3 H-chromeno[4,3-e]imidazo[1,2-a]pyrazin-3-one is described thanks to extensive use of the Buchwald–Hartwig N-arylation reaction. The acidic hydrolysis of these derivatives then gave solutions of the corresponding luciferin analogues, which were studied. Not too unexpectedly, even if these were “dressed” with substituents found in actual substrates of the nanoKAZ/NanoLuc luciferase, no bioluminescence was observed with these compounds. However, in a phosphate buffer, all produced a light signal, by chemiluminescence, with extensive variations in their respective intensity and this could be increased by adding a quaternary ammonium salt in the buffer. This aspect was actually instrumental to determine the emission spectra of many of these luciferin analogues.
Zeolite (Y-H)-based green synthesis, antimicrobial activity, and molecular docking studies of imidazole bearing oxydibenzene hybrid molecules
Ahmad, Iqrar,Desai, Nisheeth C.,Jethawa, Aratiba M.,Maheta, Abhay S.,Pandit, Unnat P.,Patel, Harun
supporting information, (2021/12/23)
In this green synthesis, zeolite (Y-H) appears to be an intriguing choice for obtaining a high yield with a shorter reaction time. In addition, we have synthesized N-aryl-(4-benzylidene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl)-3-phenoxybenzamides (4a-i), which will be proved to be potent antimicrobial agents. The title compounds were tested against Gram-positive, Gram-negative, and fungal strains using the Mueller–Hinton Broth technique. N-(4-benzylidene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl)-3-phenoxybenzamide (4a) (minimum inhibitory concentration [MIC]?=?25 μg/mL, S. pyogenes) and N-(4-[4-fluorobenzylidene]-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl)-3-phenoxybenzamide (4f) (MIC?=?100 μg/mL, C. albicans, A. niger, A. clavatus) were the most effective against Gram-positive and Gram-negative bacteria as well as fungal strains. To understand the mechanism of action of synthesized compounds, molecular docking experiments were performed against S. aureus tyrosyl-tRNA synthetase and C. albicans sterol 14-α demethylase.
Synthesis and in vitro carbonic anhydrases and acetylcholinesterase inhibitory activities of novel imidazolinone-based benzenesulfonamides
Tugrak, Mehtap,Gul, Halise Inci,Demir, Yeliz,Levent, Serkan,Gulcin, Ilhami
, (2020/12/09)
New imidazolinone-based benzenesulfonamides 3a–e and 4a–e were synthesized in three steps?and their chemical structures were confirmed by 1H NMR (nuclear magnetic resonance), 13C NMR, and high-resolution mass spectrometry. The benzenesulfonamides used were sulfacetamide (3a, 4a), sulfaguanidine (3b, 4b), sulfanilamide (3c, 4c), sulfadiazine (3d, 4d), sulfamerazine (3e), and sulfathiazole (4e). The compounds were evaluated against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes to obtain possible drug candidate/s. The lead compounds of the series were 3a and 4a against human CA (hCA) I, whereas?3d and 4a were leads against hCA II in terms of Ki values. Series 4 includes more effective CAs inhibitors than series 3 (except 3d). Series 4 compounds having a nitro group (except 4d) were 3.3–4.8 times more selective inhibitors than their corresponding analogues 3a–d in series 3, in which hydrogen was located in place of the nitro group, by considering Ki values against hCA II. Compounds 3c and 4c, where the sulfanilamide moiety is available, were the leads in terms of AChE inhibition with the lowest Ki values. The use of secondary sulfonamides was a more effective modification on CA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.
Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition
Ghanim, Amany M.,Rezq, Samar,Ibrahim, Tarek S.,Romero, Damian G.,Kothayer, Hend
, (2021/04/23)
Based on the observed pharmacophoric structural features for the reported dual COX/15-LOX inhibitors and inspired by the abundance of COX/LOX inhibitory activities reported for the 1,2,4-triazine and quinoline scaffolds, we designed and synthesized novel 1,2,4-triazine-quinoline hybrids (8a-n). The synthesized hybrids were evaluated in vitro as dual COXs/15-LOX inhibitors. The new triazine-quinoline hybrids (8a-n) exhibited potent COX-2 inhibitory profiles (IC50 = 0.047–0.32 μM, SI ～ 20.6–265.9) compared to celecoxib (IC50 = 0.045 μM, SI ～ 326). Moreover, they revealed potent inhibitory activities against 15-LOX enzyme compared to reference quercetin (IC50 = 1.81–3.60 vs. 3.34 μM). Hybrid 8e was the most potent and selective dual COX-2/15-LOX inhibitor (COX-2 IC50 = 0.047 μM, SI = 265.9, 15-LOX IC50 = 1.81 μM). These hybrids were further challenged by their ability to inhibit NO, ROS, TNF-α, IL-6 inflammatory mediators, and 15-LOX product, 15-HETE, production in LPS-activated RAW 264.7 macrophages cells. Compound 8e was the most potent hybrid in reducing ROS and 15-HETE levels showing IC50 values of 1.02 μM (11-fold more potent than that of celecoxib, IC50 = 11.75 μM) and 0.17 μM (about 43 times more potent than celecoxib, IC50 = 7.46 μM), respectively. Hybrid 8h exhibited an outstanding TNF-α inhibition with IC50 value of 0.40 μM which was about 25 times more potent than that of celecoxib and diclofenac (IC50 = 10.69 and 10.27 μM, respectively). Docking study of the synthesized hybrids into the active sites of COX-2 and 15-LOX enzymes ensures their favored binding affinity. To our knowledge, herein we reported the first 1,2,4-triazine-quinoline hybrids as dual COX/15-LOX inhibitors.
Discovery of a necroptosis inhibitor improving dopaminergic neuronal loss after mptp exposure in mice
Oliveira, Sara R.,Dionísio, Pedro A.,Gaspar, Maria M.,Ferreira, Maria B. T.,Rodrigues, Catarina A. B.,Pereira, Rita G.,Estev?o, Mónica S.,Perry, Maria J.,Moreira, Rui,Afonso, Carlos A. M.,Amaral, Joana D.,Rodrigues, Cecília M. P.
, (2021/05/21)
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, mainly characterized by motor deficits correlated with progressive dopaminergic neuronal loss in the substantia nigra pars compacta (SN). Necroptosis is a caspase-independent f
Novel Approach to the Synthesis of 3-amino-4-arylpyridin-2(1H)-one Derivatives
Chernenko, Sergei А.,Dmitriev, Maksim V.,Fisyuk, Alexander S.,Samsonenko, Anna L.,Shatsauskas, Anton L.,Shuvalov, Vladislav Yu.
, p. 764 - 771 (2021/10/04)
[Figure not available: see fulltext.] The reaction of 4-arylidene-2-phenyloxazol-5(4H)-ones with enamines of ethyl acetoacetate gave 4-aryl-2-methyl-6-oxo-5-[(phenylcarbonyl)amino]-1,4,5,6-tetrahydropyridine-3-carboxylic acid esters, which, when heated with phosphorus oxychloride, were converted into esters of 7-aryl-5-methyl-2-phenyloxazolo[5,4-b]pyridine-6-carboxylic acids. Alkaline hydrolysis of these compounds gave 4-aryl-2-methyl-6-oxo-5-[(phenylcarbonyl)amino]-1,6-dihydropyridine-3-carboxylic acid esters.
Design, Synthesis, and Antimicrobial Activity of Novel Fluorine-Containing Imidazolones
Desai,Wadekar,Mehta,Pandit
, p. 976 - 985 (2021/08/09)
Abstract: A simple synthetic protocol have been developed for the preparation of novelN-(4-benzylidene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl)-N′-phenylthiourea derivatives by the reaction of4-benzylidene-2-phenyl-4,5-dihydro-1,3-oxazol-5-ones with N
Nickel-Catalyzed Asymmetric Hydrogenation of 2-Amidoacrylates
Chen, Jianzhong,Gridnev, Ilya D.,Hu, Yawen,Li, Bowen,Zhang, Wanbin,Zhang, Zhenfeng
supporting information, p. 5371 - 5375 (2020/02/15)
Earth-abundant nickel, coordinated with a suitable chiral bisphosphine ligand, was found to be an efficient catalyst for the asymmetric hydrogenation of 2-amidoacrylates, affording the chiral α-amino acid esters in quantitative yields and excellent enantioselectivity (up to 96 % ee). The active catalyst component was studied by NMR and HRMS, which helped us to realize high catalytic efficiency on a gram scale with a low catalyst loading (S/C=2000). The hydrogenated products could be simply converted into chiral α-amino acids, β-amino alcohols, and their bioactive derivatives. Furthermore, the catalytic mechanism was investigated using deuterium-labeling experiments and computational calculations.
Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress
Abdel-Bakky, Mohamed S.,Abdelghany, Tamer M.,Ahmed, Hany E. A.,Ahmed, Mostafa H.,Boothello, Rio,El-Araby, Moustafa E.,Elhaggar, Radwan S.,Malebari, Azizah M.,Omar, Abdelsattar M.,Patel, Bhaumik B,Safo, Martin K.
, (2020/06/01)
Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 μM), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido)propenamide] 45 killed colon cancer cells at IC50 = 0.89 μM (Caco-2), 2.85 μM (HCT-116) and 1.65 μM (HT-29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 μM and 77.6 μM, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with prominent selectivity profile over non-cancerous cell lines.
Synthesis, biological evaluation and in silico studies with 4-benzylidene-2-phenyl-5(4H)-imidazolone-based benzenesulfonamides as novel selective carbonic anhydrase IX inhibitors endowed with anticancer activity
Eldehna, Wagdy M.,Abdelrahman, Mohamed A.,Nocentini, Alessio,Bua, Silvia,Al-Rashood, Sara T.,Hassan, Ghada S.,Bonardi, Alessandro,Almehizia, Abdulrahman A.,Alkahtani, Hamad M.,Alharbi, Amal,Gratteri, Paola,Supuran, Claudiu T.
, (2019/07/12)
In the presented work, we report the synthesis of a series of 4-benzylidene-2-phenyl-5(4H)-imidazolone-based benzenesulfonamides 7a-f via the Erlenmeyer–Pl?chl reaction. All the prepared imidazolones 7a-f were evaluated as inhibitors of human (h) carbonic anhydrases (CA, EC 4.2.1.1) cytosolic isoforms hCA I and II, as well as transmembrane tumor-associated isoforms hCA IX and XII. All the tested hCA isoforms were inhibited by the prepared imidazolones 7a-f in variable degrees with the following KIs ranges: 673.2–8169 nM for hCA I, 61.2–592.1 nM for hCA II, 23–155.4 nM for hCA XI, and 21.8–179.6 nM for hCA XII. In particular, imidazolones 7a, 7e, and 7f exhibited good selectivity towards the tumor-associated isoforms (CAs IX and XII) over the off-target cytosolic (CAs I and II) with selectivity index (SI) in the range of 6.2–19.4 and 3.3–8, respectively. Moreover, imidazolones 7a-f were screened for their anticancer activity in one dose (10?5 M) assay against a panel of 60 cancer cell lines according to US-NCI protocol. Furthermore, 7a, 7e and 7f were evaluated for their anti-proliferative activity against colorectal cancer HCT-116 and breast cancer MCF-7 cell lines. Furthermore, 7e and 7f were screened for cell cycle disturbance and apoptosis induction in HCT-116 cells. Finally, a molecular docking study was carried out to rationalize the obtained results.
