579-93-1Relevant articles and documents
Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells
Piven, Yuri A.,Yastrebova, Margarita A.,Khamidullina, Alvina I.,Scherbakov, Alexander M.,Tatarskiy, Victor V.,Rusanova, Julia A.,Baranovsky, Alexander V.,Zinovich, Veronica G.,Khlebnicova, Tatyana S.,Lakhvich, Fedor A.
supporting information, (2021/11/30)
Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamid
Synthetic Studies toward 1,2,3,3a,4,8b-Hexahydropyrrolo[3,2-b]indole Core. Unusual Fragmentation with 1,2-Aryl Shift
Aksenov, Alexander V.,Aksenov, Dmitrii A.,Aksenov, Nicolai A.,Aksenova, Anna A.,Aleksandrova, Elena V.,Nobi, Mezvah A.,Rubin, Michael
, p. 1434 - 1444 (2022/01/27)
Base-assisted transformations of 2-(3-oxoindolin-2-yl)acetonitriles were investigated. Unexpectedly, attempted reactions of substrates possessing nonprotected nitrogen atoms were accompanied by unusual extrusions of 2-arylacetonitriles, followed by a 1,2-aryl shift to afford 3-hydroxyindolin-2-ones. On the other hand, the reactions for N-alkyl derivatives of oxoindolines took the expected route by only providing 1,2,3,3a,4,8b-hexahydropyrrolo[3,2-b]indoles.
Design, molecular docking, in vitro, and in vivo studies of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors with potential activity against hepatocellular carcinoma
Eissa, Ibrahim.H.,Ibrahim, Mohammed K.,Metwaly, Ahmed M.,Belal, Amany,Mehany, Ahmed B.M.,Abdelhady, Alsayed A.,Elhendawy, Mostafa A.,Radwan, Mohamed M.,ElSohly, Mahmoud A.,Mahdy, Hazem A.
, (2020/12/21)
A series of new VEGFR-2 inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against hepatocellular carcinoma (HepG-2 cell line). Compound 29b (IC50 = 4.33 ± 0.2 μg/ml) was found to be the most potent derivative as it has showed to be more active than doxorubicin (IC50 = 4.50 ± 0.2 μg/ml) and 78% of sorafenib activity (IC50 = 3.40 ± 0.25 μg/ml). The inhibitory profiles against VEGFR-2 were also assessed for the most promising candidates (16b, 20c, 22b, 24a, 24b, 28c, 28e, 29a, 29b and 29c). Compounds 29b, 29c and 29a exhibited potent inhibitory activities towards VEGFR-2 at IC50 values of 3.1 ± 0.04, 3.4 ± 0.05 and 3.7 ± 0.06 μM, respectively, comparing sorafenib (IC50 = 2.4 ± 0.05 μM). Furthermorer, compound 29b induced apoptosis and arrested the cell cycle growth at G2/M phase. Additionally, in vivo antitumor experiments revealed that compounds 29b and 29c have significant tumor growth inhibition. The test of immuno-histochemical expression of activated caspase-3 revealed that there is a time-dependent increase in cleaved caspase-3 protein expression upon exposure of HepG-2 cells to compound 29b. Moreover, the fibroblastic proliferative index test revealed that compound 29b could attenuate liver fibrosis. Docking studies also supported the results concluded from the biological screening via prediction of the possible binding interactions of the target compounds with VEGFR-2 active sites using the crystal structure of VEGFR-2 downloaded from the Protein Data Bank, (PDB ID: 2OH4) using Discovery Studio 2.5 software. Further structural optimization of the most active candidates may serve as a useful strategy for getting new lead compounds in search for powerful and selective antineoplastic agents.
Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers
Belal, Amany,Eissa, Ibrahim H.,El-Gamal, Kamal M. A.,El-Sharkawy, Abdou,Elhendawy, Mostafa A.,Elsohly, Mahmoud A.,Ibrahim, Mohammed K.,Mahdy, Hazem A.,Mehany, Ahmed B. M.,Metwaly, Ahmed M.,Radwan, Mohamed M.
, (2019/12/24)
Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. Accordingly, new quinazoline-based derivatives having the structural features of VEGFR-2 inhibitors were designed and synthesized. Anti-proliferative activities were evaluated against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) using MTT assay method. Doxorubicin and sorafenib were used as positive controls. Compounds 26b, 29a, 29b and 30 showed excellent anti-cancer activities against all cell lines. Moreover, compound 31 was the most active with IC 50 values of 3.97 ± 0.2, 4.83 ± 0.2 and 4.58 ± 0.3 μM, respectively. The most active cytotoxic agents were further evaluated in vitro for their VEGFR-2 inhibitory activities, compound 31 showed a high activity against VEGFR-2 with an IC50 value of 2.5 ± 0.04 μM, almost equal to that of sorafenib (IC50 = 2.4 ± 0.05 μM). Further studies revealed the ability of this promising quinazoline derivative 31 to induce apoptosis and arrest cell cycle growth at G2/M phase. In vivo antitumor activities of the synthesized compounds revealed that compounds 30 and 31 possessed significant tumor growth inhibition effect. Molecular docking studies were also performed and finally we can say that VEGFR-2 inhibition confers the reported cytotoxic activities.
Palladium catalyzed chemo- and site-selective C-H acetoxylation and hydroxylation of oxobenzoxazine derivatives
Bakthadoss, Manickam,Vijay Kumar, Polu,Kumar, Ravan,Agarwal, Vishal
supporting information, p. 4465 - 4469 (2019/05/16)
An efficient protocol for the introduction of acetoxy and hydroxy functionalities on unactivated aryl sp2 carbons of oxobenzoxazine derivatives via an ortho-C-H activation reaction using a palladium catalyst has been developed for the first tim
A straightforward TBHP-mediated synthesis of 2-amidobenzoic acids from 2-arylindoles and their antimicrobial activity
Patel, Om P.S.,Dhiman, Shiv,Khan, Shahid,Shinde, Vikki N.,Jaspal, Sonam,Srivathsa, Manu R.,Jha, Prabhat N.,Kumar, Anil
, p. 5962 - 5970 (2019/06/24)
A simple and highly efficient strategy has been developed for the synthesis of 2-amidobenzoic acids through the tert-butyl hydroperoxide (TBHP)-mediated oxygenation and sequential ring opening of 2-arylindoles in a one-pot fashion under metal-free aerobic conditions. The developed synthetic protocol is operationally simple, tolerates a wide range of functional groups, and is amenable to the gram-scale. Radical trapping experiments revealed that the reaction involves a radical pathway. The synthesized compounds (2a-s) were tested for in vitro antimicrobial activity. Among all screened compounds, 2d showed the maximum antibacterial activity against P. aerugunosa (ZOI = 17 mm, MIC = 32 μg mL-1) and compounds 2d and 2p showed the maximum (32 μg mL-1) antifungal activity against A. flavus and C. albicans.
A new series of Schiff base derivatives bearing 1,2,3-triazole: Design, synthesis, molecular docking, and α-glucosidase inhibition
Nasli-Esfahani, Ensieh,Mohammadi-Khanaposhtani, Maryam,Rezaei, Sepideh,Sarrafi, Yaghoub,Sharafi, Zeinab,Samadi, Nasser,Faramarzi, Mohammad Ali,Bandarian, Fatemeh,Hamedifar, Haleh,Larijani, Bagher,Hajimiri, Mirhamed,Mahdavi, Mohammad
, (2019/08/12)
A series of new Schiff bases bearing 1,2,3-triazole 12a?o was designed, synthesized, and evaluated as α-glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α-glucosidase and were more potent than the standard drug aca
Radical-Induced, Palladium-Catalyzed C–H Activation: An Approach to Functionalize 4H-Benzo[d][1,3]oxazin-4-one Derivatives by Using Toluenes, Aldehydes, and Benzyl Alcohols
Kumar, Prashant,Gupta, Mohit,Bahadur, Vijay,Parmar, Virinder S.,Singh, Brajendra K.
supporting information, p. 1552 - 1558 (2018/04/20)
Toluenes, aldehydes, and benzyl alcohols have been utilized in the radical-induced direct functionalization of 4H-benzo[d][1,3]oxazin-4-one derivatives by using a palladium-catalyzed C–H activation strategy. The stability, low toxicity, and ease of access
Latent Bronsted Base Solvent-Assisted Amide Formation from Amines and Acid Chlorides
Otsuka, Rikuto,Maruhashi, Kazuo,Ohwada, Tomohiko
supporting information, p. 2041 - 2057 (2018/05/04)
Weakly basic amines, including even neutral amines such as nitroaniline and aminocarboxylic acids, react with acid chlorides very efficiently in N, N -dimethylacetamide (DMAC), without addition of a base, to give the corresponding amides in high yields. The role of DMAC and related solvents as latent Bronsted bases was studied in these amidation reactions. Less basic amines, such as aromatic amines, reacted with benzoyl chloride faster than more basic aliphatic amines.
Aminobenzoic acid derivatives as antioxidants and cholinesterase inhibitors; synthesis, biological evaluation and molecular docking studies
Iftikhar, Kiran,Murtaza, Shahzad,Kousar, Naghmana,Abbas, Aadil,Tahir, Muhammad Nawaz
, p. 385 - 396 (2018/04/23)
Cholinesterase namely, acetyl- and butyrylcholinesterase (AChE and BChE, respectively), has been recognized as a primary class of enzyme that hydrolyzes the acetylcholine (ACh) neurotransmitter in synaptic junctions. Diminished levels of the neurotransmitter in synaptic junction lead to Alzheimerís disease (AD). Inhibition of cholinesterase is thus, an attractive strategy for AD treatment. The study includes the synthesis and characterization of a series of 2-, 3- and 4-aminobenzoic acid derivatives (1a?5c), their biological screening against cholinesterase enzyme and molecular docking study to demonstrate putative binding modes. Antioxidant potential of the synthesized series was also determined. The cholinesterase enzyme inhibition assay showed that compound 5b has the highest inhibition potential against acetylcholinesterase with an IC50 value of 1.66 ± 0.03 μM while in case of butyrylcholinesterase, compound 2c has the highest inhibitory potential with an IC50 value of 2.67 ± 0.05 μM. Molecular docking studies supports the results of enzyme inhibition potential with binding energy value ?G = -9.54 Kcal mol-1 for compound 5b in case for acetylcholinesterase while for butyrylcholinesterase, ?G = -5.53 Kcal mol-1 was obtained for compound 2c. The synthesized series of compounds also shows mild to moderate antioxidant potential. The benzoyl- containing compounds shows better antioxidant activity as compared to other derivatives of the synthesized series. Based on the molecular docking studies and enzyme inhibition potential, the synthesized series of compounds can be regarded as potent cholinesterase inhibitors and can be used for designing and synthesizing more potent drugs for Alzheimerís disease and neurodegenerative diseases.
