- Synthesis and colon anticancer activity of some novel thiazole/-2-quinolone derivatives
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We direct for the synthesis of 1,6,7-trisubstituted-4-phenylthiazol-2(3H)-ylidene)hydrazono)methyl)quinolin-2-one derivatives by the reaction of corresponding thiosemicarbazone derived by 2-quinolone derivatives with 2-bromoacetophenones in presence of triethylamine at room temperature. The mechanism of the formed products was discussed. The structure of the obtained products was fully characterized using different spectral techniques including infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS) together with elemental analyses. The new synthesized compounds showed a moderate colon anticancer activity.
- Aly, Ashraf A.,Mohamed, Asmaa H.,Ramadan, Mohamed
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- One-step Synthesis of 3-Unsubstituted 4-Hydroxy-2(1H)-Quinoline
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3-Unsubstituted 4-hydroxy-2(1H)-quinolone (DHQ) derivatives were synthesized from aniline derivatives and diethyl malonate at low temperature using AlCl3 as catalyst and Eaton reagent as acidic environment. A reaction mechanism was proposed and elucidated. Different synthetic intermediates are specially prepared or purified and used to understand the reaction and validation mechanism.
- Menglin, Ma,Qingrong, Sun,Weiqing, Yang,Xingyi, Wang,Yinan, Xu
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p. 435 - 441
(2021/11/22)
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- Identification and molecular modeling of new quinolin-2-one thiosemicarbazide scaffold with antimicrobial urease inhibitory activity
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Abstract: A new series of 6-substituted quinolin-2-one thiosemicarbazides 6a–j has been synthesized. The structure of the target compounds was proved by different spectroscopic and elemental analyses. All the designed final compounds were evaluated for their in vitro activity against the urease-producing R. mucilaginosa and Proteus mirabilis bacteria as fungal and bacterial pathogens, respectively. Moreover, all compounds were in vitro tested as potential urease inhibitors using the cup-plate diffusion method. Compounds 6a and 6b were the most active with (IC50 = 0.58 ± 0.15 and 0.43 ± 0.09?μM), respectively, in comparison with lead compound I (IC50 = 1.13 ± 0.00?μM). Also, the designed compounds were docked into urease proteins (ID: 3LA4 and ID: 4UBP) using Open Eye software to understand correctly about ligand–receptor interactions. The docking results revealed that the designed compounds can interact with the active site of the enzyme through multiple strong hydrogen bonds. Moreover, rapid overlay of chemical structures’ analysis was described to understand the 3D QSAR of synthesized compounds as urease inhibitors. The results emphasize the importance of polar thiosemicarbazide directly linked to 6-substituted quinolone moieties as promising antimicrobial urease inhibitors. Graphic abstract: [Figure not available: see fulltext.]
- Elbastawesy, Mohammed A. I.,El-Shaier, Yaseen A. M. M.,Ramadan, Mohamed,Brown, Alan B.,Aly, Ashraf A.,Abuo-Rahma, Gamal El-Din A.
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- New Quinoline-2-one/thiazolium bromide Derivatives; Synthesis, Characterization and Mechanism of Formation
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We report on the formation of new quinoline-2-one derived by thiazolium bromides from the reaction of 3-thiosemicarbazides derived by 2-quinolones with 2-bromoacetophenones. The structure of products was elucidated by mass, IR and NMR spectra together with elemental analysis. The mechanism of products formation was discussed.
- Mostafa, Sara M.,Aly, Ashraf A.,Sayed, Samia M.,Raslan, Mohamed A.,Ahmed, Amira E.,Nafady, Ayman,Ishak, Esam A.,Shawky, Ahmed M.,Abdelhafez, El-Shimaa M.N.
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- Method for preparing 4-hydroxyquinolin-2(1H)-one compound
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The invention discloses a method for preparing a 4-hydroxyquinolin-2(1H)-one compound, which comprises the following steps of: reacting 2-ethynylaniline as shown in a formula (1) and carbon dioxide which are used as raw materials in an ionic liquid in the presence of a silver salt catalyst to obtain the 4-hydroxyquinoline-2 (1H)-one compound as shown in a formula (II). The reaction equation is shown in the specification. When the method disclosed by the invention is applied to the reaction for preparing the 4-hydroxyquinolin-2(1H)-one compound, the reaction conditions are relatively mild, the dosage of the silver salt catalyst is small, the separation and purification process of the product is relatively simple, the product yield is high, and the application range of a substrate is wide.
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Paragraph 0067-0069
(2021/09/22)
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- Arylidenes of Quinolin-2-one scaffold as Erlotinib analogues with activities against leukemia through inhibition of EGFR TK/ STAT-3 pathways
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A new series of 6-substiuted-4-(2-(4-substituted-benzylidene)hydrazinyl)quinolin-2(1H)-one derivatives have been designed and synthesized. The structure of the synthesized compounds was proved by 1H NMR, 13C NMR, 2D NMR, mass and elemental analyses. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI protocol. Consequently, the most active compounds were further examined against the most sensitive leukemia RPMI-8226 and on healthy cell lines. 6-Chloro-derivative was the most active one; with IC50 = 15.72 ± 1.21 and 46.05 ± 2.36 μM against RPMI-8226 and normal cell lines, respectively. Also, it showed a remarkable inhibitory activity compared to gefitinib on the EGFR TK mutant, wild and on H-RAS in addition to STAT-3 with IC50 = 695.49 ± 21.8, 263.15 ± 15.13, 10.61 ± 0.27 and 1.753 ± 0.81 nM, respectively. Cell cycle analysis of RPMI-8226 cells treated with the 6-chloro-derivative showed cell cycle arrest at G2/M phase (supported by Caspases-3,8, BAX and Bcl-2 studies) with a significant pro-apoptotic activity as indicated by annexin V-FITC staining. Moreover, the docking studies ROCS analysis and Tanimoto scores supported the results. The study illustrated the effect of several factors on compounds activity.
- Abuo-Rahma, Gamal El-Din A.,Aly, Ashraf A.,El-Shaier, Yaseen A. M. M.,Elbastawesy, Mohammed A. I.,Ramadan, Mohamed
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- Novel Pyrazoloquinolin-2-ones: Design, synthesis, docking studies, and biological evaluation as antiproliferative EGFR-TK inhibitors
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Two new series of diethyl 2-[2-(substituted-2-oxo-1,2-dihydroquinolin-4-yl)hydrazono]-succinates 6a-g and 1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazoles 7a-f have been designed and synthesized. The structures of the synthesized compounds were proved by IR, mass, NMR (2D) spectra and elemental analyses. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI protocol. Consequently, seven compounds were further examined against the most sensitive cell lines, leukemia CCRF-CEM, and MOLT-4. 5-Amino-1-(6-bromo-2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazole-3,4-dicarbonitrile (7f) was the most active product, with IC50 = 1.35 uM and 2.42 uM against MOLT-4 and CCRF-CEM, respectively. Also, it showed a remarkable inhibitory activity compared to erlotinib on the EGFR TK with IC50 = 247.14 nM and 208.42 nM, respectively. Cell cycle analysis of MOLT-4 cells treated with 7f showed cell cycle arrest at G2/M phase (supported by Caspases, BAX and Bcl-2 studies) with a significant pro-apoptotic activity as indicated by annexin V-FITC staining. Moreover, the docking study indicated that both the pyrazole moiety and the quinolin-2-one ring showed good fitting into EGFR (PDB code: 1M17). In order to interpret SAR of the designed compounds, and provide a basis for further optimization, molecular docking of the synthesized compounds to known EGFR inhibitors was performed. The study illustrated the effect of several factors on the compounds’ activity.
- Elbastawesy, Mohammed A.I.,Aly, Ashraf A.,Ramadan, Mohamed,Elshaier, Yaseen A.M.M.,Youssif, Bahaa G.M.,Brown, Alan B.,El-Din A Abuo-Rahma, Gamal
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- Compounds having anticonvulsion activity, preparing methods thereof and applications of the compounds
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The invention provides 7-substituted-5-methyl-1,2,4-triazolo[4,3-a] quinoline and 7-substituted-5-ethoxy-[1,2,4]-triazolo[4,3-a] quinoline compounds having anticonvulsion activity, preparing methods thereof and applications of the compounds in the field of preparing anticonvulsion medicines.
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Paragraph 0082; 0083; 0084; 0085
(2017/10/05)
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- Natural Product-Mimetic Scaffolds with Privileged Heterocyclic Systems: Design, Synthesis, and Evaluation of Antioxidant Activity of Quinazoquinobenzothiazinones
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(Chemical Equation Presented) Structurally diverse quinazolinoquinolinobenzothiazinones based on rutaecarpine structural framework with hybrid structural features of three medicinally privileged heterocyclic systems has been synthesized as natural product-mimetic scaffolds involving the use of multi-step reaction sequences. The synthesized quinazolinoquinolinobenzothiazinones have been evaluated for their antioxidant and radical scavenging activities.
- Sharma, Kshitija,Khandelwal, Sarita,Samarth,Kumar, Mahendra
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p. 220 - 228
(2016/02/10)
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- Synthesis and SAR studies of novel 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives for anticancer activity
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Background and Purpose 4-Phenylquinolin-2(1H)-one (4-PQ) derivatives can induce cancer cell apoptosis. Additional new 4-PQ analogs were investigated as more effective, less toxic antitumour agents. Experimental Approach Forty-five 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives were synthesized. Antiproliferative activities were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliun bromide assay and structure-activity relationship correlations were established. Compounds 9b, 9c, 9e and 11e were also evaluated against the National Cancer Institute-60 human cancer cell line panel. Hoechst 33258 and Annexin V-FITC/PI staining assays were used to detect apoptosis, while inhibition of microtubule polymerization was assayed by fluorescence microscopy. Effects on the cell cycle were assessed by flow cytometry and on apoptosis-related proteins (active caspase-3, -8 and -9, procaspase-3, -8, -9, PARP, Bid, Bcl-xL and Bcl-2) by Western blotting. Key Results Nine 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives (7e, 8e, 9b, 9c, 9e, 10c, 10e, 11c and 11e) displayed high potency against HL-60, Hep3B, H460, and COLO 205 cancer cells (IC50 50 > 50 μM). Particularly, compound 11e exhibited nanomolar potency against COLO 205 cancer cells. Mechanistic studies indicated that compound 11e disrupted microtubule assembly and induced G2/M arrest, polyploidy and apoptosis via the intrinsic and extrinsic signalling pathways. Activation of JNK could play a role in TRAIL-induced COLO 205 apoptosis. Conclusion and Implications New quinolone derivatives were identified as potential pro-apoptotic agents. Compound 11e could be a promising lead compound for future antitumour agent development.
- Chen, Yi-Fong,Lin, Yi-Chien,Morris-Natschke, Susan L.,Wei, Chen-Fang,Shen, Ting-Chen,Lin, Hui-Yi,Hsu, Mei-Hua,Chou, Li-Chen,Zhao, Yu,Kuo, Sheng-Chu,Lee, Kuo-Hsiung,Huang, Li-Jiau
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supporting information
p. 1195 - 1221
(2015/03/04)
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- Synthesis of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4-dihydro- 1H-quinolin-2-ones, as novel quinoline derivatives with antibacterial activity
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A novel series of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4- dihydro-1H-quinolin-2-ones was synthesized and tested as antimicrobials. The minimum inhibitory concentration (MIC) values of the most active heterocycles were slightly higher than those exhibited by levofloxacin, employed as comparator. Structural factors affecting the activity were explored along three diversification points, including the substituents of the aromatic rings of the 3-benzyl moieties, as well as the functionalization of both, the homocyclic ring of the heterocycle and the quinolonic nitrogen atom. 6-Chloro and 3,3-bis(4′-chlorobenzyl) derivatives showed the lower MIC values. Optimally substituted heterocycles were synthesized, which exhibited enhanced activity.
- Ferretti, Matías D.,Neto, Alexandre T.,Morel, Ademir F.,Kaufman, Teodoro S.,Larghi, Enrique L.
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p. 253 - 266
(2014/06/09)
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- Synthesis and antioxidant activity of quinolinobenzothiazinones
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A new series of structurally diverse quinolinobenzothiazinones has been synthesized with the annulation of heterocyclic structural pharmacophores. The synthesized quinolinobenzothiazinones have been evaluated for their antioxidant (LPO & GSH) and radical scavenging activities (DPPH and ABTS assays).
- Kumar,Sharma, Kshitija,Samarth,Kumar
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scheme or table
p. 4467 - 4472
(2010/10/19)
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- Clean and convenient one-pot synthesis of 4-hydroxycoumarin and 4-hydroxy-2-quinolinone derivatives
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A simple, efficient, and environmentally friendly procedure has been developed for the reaction of Meldrum's acid with phenol, substituted phenols, aniline, or substituted anilines with Eaton's reagent (phosphoric anhydride+methylsulfonic acid) as cyclization reagent. 4-Hydroxycoumarins and 4-hydroxy-2-quinolinones were synthesized in moderate yields by carrying out the reaction in solvent-free, convenient, and clean one-pot preparation.
- Gao, Wen-Tao,Hou, Wen-Duan,Zheng, Mei-Ru,Tang, Li-Jun
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experimental part
p. 732 - 738
(2011/03/17)
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- Compounds with anti-cancer activity
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Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and/or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and/or other types of anti-cancer reagents.
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Page/Page column 82
(2008/12/08)
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- Quinone methide reactions: Synthesis of novel pyranodiquinolines
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The reaction of alkaline 4-hydroxyquinolin-2(1H)-ones (1) with vinyl acetate has been studied.Interestingly, 1,1-diquonolinoethane formed via a quinoline-quinone methide intermediate undergoes dehydration in situ by two paths yielding the isomeric 7-methylpyranodiquinolines (3 and 4).
- Balasubramanian, C.,Kumaraswami, K.,Dharmaraj, N.,Mohan, P. S.
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p. 460 - 462
(2007/10/02)
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- Quinoline Alkaloids. Synthesis of Khaplofoline, Ribalinine, and Flindersine
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Reaction of 4-hydroxy-3-prenylquinolin-2(1H)one (5a) with iodine and silver acetate gave a iodopyranoquinoline (6a), which was then converted into the alkaloids khaplofoline (1) and ribalinine (2).Reaction of 5a with iodine and mercuric oxide afforded a mixture of 6a and its angular isomer 7a; the conversion of latter into flindersine (10) is described.Keywords: Pyranoquinoline Alkaloids, Khaplofoline, Ribalinine, Flindersine
- Subramanian, M.,Mohan, P. S.,Shanmugam, P.,Prasad, K. J. Rajendra
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p. 1016 - 1020
(2007/10/02)
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