525-76-8Relevant articles and documents
Synthesis, biological activity and preliminary in silico ADMET screening of polyamine conjugates with bicyclic systems
Szumilak, Marta,Galdyszynska, Malgorzata,Dominska, Kamila,Bak-Sypien, Irena I.,Merecz-Sadowska, Anna,Stanczak, Andrzej,Karwowski, Boleslaw T.,Piastowska-Ciesielska, Agnieszka W.
, (2017)
Polyamine conjugates with bicyclic terminal groups including quinazoline, naphthalene, quinoline, coumarine and indole have been obtained and their cytotoxic activity against PC-3, DU-145 and MCF-7 cell lines was evaluated in vitro. Their antiproliferative potential differed markedly and depended on both their chemical structure and the type of cancer cell line. Noncovalent DNA-binding properties of the most active compounds have been examined using ds-DNA thermal melting studies and topo I activity assay. The promising biological activity, DNA intercalative binding mode and favorable drug-like properties of bis(naphthalene-2-carboxamides) make them a good lead for further development of potential anticancer drugs.
Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3 H)-one
Bouley, Renee,Kumarasiri, Malika,Peng, Zhihong,Otero, Lisandro H.,Song, Wei,Suckow, Mark A.,Schroeder, Valerie A.,Wolter, William R.,Lastochkin, Elena,Antunes, Nuno T.,Pi, Hualiang,Vakulenko, Sergei,Hermoso, Juan A.,Chang, Mayland,Mobashery, Shahriar
, p. 1738 - 1741 (2015)
In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.
Novel quinolinone–pyrazoline hybrids: synthesis and evaluation of antioxidant and lipoxygenase inhibitory activity
Kostopoulou, Ioanna,Diassakou, Antonia,Kavetsou, Eleni,Kritsi, Eftichia,Zoumpoulakis, Panagiotis,Pontiki, Eleni,Hadjipavlou-Litina, Dimitra,Detsi, Anastasia
, p. 723 - 740 (2020/02/25)
Abstract: The present project deals with the investigation of structure–activity relationship of several quinolinone–chalcone and quinolinone–pyrazoline hybrids, in an effort to discover promising antioxidant and anti-inflammatory agents. In order to accomplish this goal, four bioactive hybrid quinolinone–chalcone compounds (8a–8d) were synthesized via an aldol condensation reaction, which were then chemically modified, forming fifteen new pyrazoline analogues (9a–9o). All the synthesized analogues were in vitro evaluated in terms of their antioxidant and soybean lipoxygenase (LOX) inhibitory activity. Among all the pyrazoline derivatives, compounds 9b and 9m were found to possess the best combined activity, whereas 9b analogue exhibited the most potent LOX inhibitory activity, with IC50 value 10?μM. The in silico docking results revealed that the synthetic pyrazoline analogue 9b showed high AutoDock Vina score (? 10.3?kcal/mol), while all the tested derivatives presented allosteric interactions with the enzyme. Graphic Abstract: [Figure not available: see fulltext.]
Design, Synthesis, and Structure-Activity Relationship of Quinazolinone Derivatives as Potential Fungicides
Peng, Jing-Wen,Yin, Xiao-Dan,Li, Hu,Ma, Kun-Yuan,Zhang, Zhi-Jun,Zhou, Rui,Wang, Yu-Ling,Hu, Guan-Fang,Liu, Ying-Qian
, p. 4604 - 4614 (2021/05/06)
Plant diseases caused by phytopathogenic fungi reduce the yield and quality of crops. To develop novel antifungal agents, we designed and synthesized eight series of quinazolinone derivatives and evaluated their anti-phytopathogenic fungal activity. The bioassay results revealed that compounds KZL-15, KZL-22, 5b, 6b, 6c, 8e, and 8f exhibited remarkable antifungal activity in vitro. Especially, compound 6c displayed the highest bioactivity against Sclerotinia sclerotiorum, Pellicularia sasakii, Fusarium graminearum, and Fusarium oxysporum, displaying appreciable IC50 values (50% inhibitory concentration) of 2.46, 2.94, 6.03, and 11.9 μg/mL, respectively. A further mechanism interrogation revealed abnormal mycelia, damaged organelles, and changed permeability of cell membranes in S. sclerotiorum treated with compound 6c. In addition, the in vivo bioassay indicated that compound 6c possessed comparable curative and protective effects (87.3 and 90.7%, respectively) to the positive control azoxystrobin (89.5 and 91.2%, respectively) at 100 μg/mL concentration against S. sclerotiorum. This work validated the potential of compound 6c as a new and promising fungicide candidate, contributing to the exploration of potent antifungal agents.
Cytotoxicity and Antibacterial Evaluation of O-Alkylated/Acylated Quinazolin-4-one Schiff Bases
Manhas, Neha,Singh, Parvesh,Mocktar, Chunderika,Singh, Moganavelli,Koorbanally, Neil
, (2021/04/29)
A series of quinazolin-4-one Schiff bases were synthesized and tested in vitro for their cytotoxicity against two cancerous cell lines (MCF-7, Caco-2) and a human embryonic cell line (HEK-293) including their antibacterial evaluation against two Gram-positive and four Gram-negative bacterial strains. Most of the quinazoline-Schiff bases exhibited potent cytotoxicity against Caco-2. 3-[(Z)-({4-[(But-2-yn-1-yl)oxy]phenyl}methylidene)amino]-2-methylquinazolin-4(3H)-one (6f) with the O-butyne functional group displayed three-fold higher cytotoxic activity (IC50=376.8 μM) as compared to 5-fluorouracil (5-FU; IC50=1086.1 μM). However, all compounds were found to be toxic to HEK-293, except for 3-[(Z)-({4-[(2,4-difluorophenyl)methoxy]phenyl}methylidene)amino]-2-methylquinazolin-4(3H)-one (6h) that showed ～three-fold lower toxicity and higher selectivity index than 5-FU. Structure–activity relationship (SAR) analysis revealed that O-alkylation generally increased the anticancer activity and selectivity of quinazoline-4-one Schiff bases toward Caco-2 cells. The fluorinated Schiff-base generally exhibited even more significant cytotoxic activity compared to their chlorine analogs. Surprisingly, none of the quinazoline-4-one Schiff bases displayed encouraging antibacterial activity against the bacterial strains investigated. Most of the compounds were predicted to show compliance with the Lipinski parameters and ADMET profiles, indicating their drug-like properties.
Pd-Catalyzed Carbonylative Synthesis of 4H-Benzo[d][1,3]Oxazin-4-Ones Using Benzene-1,3,5-Triyl Triformate as the CO Source
Zheng, Yan,Dong, Mengke,Qu, Erdong,Bai, Jin,Wu, Xiao-Feng,Li, Wanfang
, p. 16219 - 16224 (2021/10/06)
A facile synthesis of 4H-benzo[d][1,3]oxazin-4-one derivatives by Pd-catalyzed carbonylative cross-coupling between N-(ortho-bromoaryl)amides and benzene-1,3,5-triyl triformate (TFBen) was developed. This procedure does not require the toxic and flammable gas CO as the carbonyl source and tolerates a wide scope of functional groups. Remarkably, 4H-benzo[d][1,3]oxazin-4-ones incorporated to natural products and drugs can be constructed by this method.
Recyclable palladium-catalyzed carbonylative annulation of 2-iodoanilines with acid anhydrides: A practical synthesis of 2-alkylbenzoxazinones
Zhou, Zebiao,Huang, Bin,Cai, Mingzhong
, p. 3150 - 3163 (2021/08/30)
A highly efficient heterogeneous palladium-catalyzed carbonylative annulation of 2-iodoanilines and acid anhydrides has been developed. The reaction proceeds effectively in toluene using N,N-diisopropylethylamine (DiPEA) as the base at 100 °C under 2 bar of CO and provides a novel, general, and practical method for the assembly of a wide variety of 2-alkylbenzoxazinones with high functional group tolerance and good to excellent yields. This supported palladium complex can be readily separated from the product and recovered by a simple filtration of the reaction solution and reused up to seven times with almost consistent catalytic efficiency.
Activity-directed expansion of a series of antibacterial agents
Chow, Shiao,Clarke, Justin E.,Leggott, Abbie,Nelson, Adam,O'Neill, Alex J.,Warriner, Stuart L.
supporting information, p. 8047 - 8050 (2020/08/03)
The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL-1 (i.e. 38 nM) to 2-4 μg mL-1 against S. aureus ATCC29213. This journal is
Exploration of the Structural Space in 4(3 H)-Quinazolinone Antibacterials
Qian, Yuanyuan,Allegretta, Giuseppe,Janardhanan, Jeshina,Peng, Zhihong,Mahasenan, Kiran V.,Lastochkin, Elena,Gozun, Melissa Malia N.,Tejera, Sara,Schroeder, Valerie A.,Wolter, William R.,Feltzer, Rhona,Mobashery, Shahriar,Chang, Mayland
, p. 5287 - 5296 (2020/06/10)
We report herein the syntheses of 79 derivatives of the 4(3H)-quinazolinones and their structure-activity relationship (SAR) against methicillin-resistant Staphylococcus aureus (MRSA). Twenty one analogs were further evaluated in in vitro assays. Subsequent investigation of the pharmacokinetic properties singled out compound 73 ((E)-3-(5-carboxy-2-fluorophenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one) for further study. The compound synergized with piperacillin-tazobactam (TZP) both in vitro and in vivo in a clinically relevant mouse model of MRSA infection. The TZP combination lacks activity against MRSA, yet it synergized with compound 73 to kill MRSA in a bactericidal manner. The synergy is rationalized by the ability of the quinazolinones to bind to the allosteric site of penicillin-binding protein (PBP)2a, resulting in opening of the active site, whereby the β-lactam antibiotic now is enabled to bind to the active site in its mechanism of action. The combination effectively treats MRSA infection, for which many antibiotics (including TZP) have faced clinical obsolescence.
Recyclable Heterogeneous Palladium-Catalyzed Cyclocarbonylation of 2-Iodoanilines with Acyl Chlorides in the Biomass-Derived Solvent 2-Methyltetrahydrofuran
Hao, Wenyan,Xu, Zhaotao,Zhou, Zebiao,Cai, Mingzhong
, p. 8522 - 8532 (2020/07/16)
A highly efficient, green palladium-catalyzed cyclocarbonylation of 2-iodoanilines with acyl chlorides has been developed that proceeds smoothly in a biomass-derived solvent 2-methyltetrahydrofuran with N,N-diisopropylethylamine as base at 100 °C under 20 bar of carbon monoxide using an 2-aminoethylamino-modified MCM-41-anchored palladium acetate complex [2N-MCM-41-Pd(OAc)2] as a heterogeneous catalyst, yielding a wide variety of 2-substituted 4H-3,1-benzoxazin-4-one derivatives in good to excellent yields. This supported palladium catalyst could be facilely obtained by a two-step procedure from easily available starting materials and readily recovered via a simple filtration process and recycled at least 8 times without any apparent decrease in catalytic efficiency. The developed methodology not only avoids the use of toxic solvents such as tetrahydrofuran and dimethylformamide but also solves the basic problem of expensive palladium catalyst recovery and reuse and prevents effectively palladium contamination of the desired product.
