- 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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- 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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- 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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- Synthesis, crystal structure, cytotoxic and apoptotic activity of 2,4-dichloro-6-methylquinoline on human oral carcinoma cell line
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The present report describes the synthesis, IR spectra, 3-dimensional structure of the compound 2,4-dichloro-6-methylquinoline and evaluation of its anti-cancer activity using propidium iodide (PI) staining and annexin binding assay techniques. This derivative of quinoline was synthesized from the mixture of p-toluidine and malonic acid and synthesis has been achieved in a one-pot reaction from an aryl amine, malonic acid and phosphorous oxychloride. Crystallographic data reveals that the crystals belong to triclinic crystal system with space group P-1 with the unit cell dimensions of a = 7.14(1) A, b = 11.53(1) A, c = 11.97(1) A and α = 90.18° (10), β = 106.31° (10), γ = 91.07° (10). The in vitro anti-cancer assay indicated that compound has cytotoxic and apoptotic activity on human oral squamous carcinoma (KB) cell line, thus it could be developed as a potent anti-cancer agent. Synthesis, Crystal Structure, Cytotoxic and Apoptotic Activity of 2,4-Dichloro-6-methylquinoline on Human Oral Carcinoma Cell Line R. K. Somvanshia, R. Subashinib, V. Dhanasekaranb, G. Arulprakashb, S. N. Dasc, S. Deya [Figure not available: see fulltext.]
- Somvanshi,Subashini,Dhanasekaran,Arulprakash,Das,Dey
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- Synthesis, characterization, pharmacological, molecular modeling and antimicrobial activity evaluation of novel isomer quinoline derivatives
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The structural and spectroscopic characteristics of the synthesized structurally novel compound 4-chloro-6-methylquinoline-2(1H)-one (4C6MQ) and its isomer 4-chloro-8-methylquinoline-2(1H)-one (4C8MQ) have been examined by means of experimental and computational quantum chemical methods like density functional theory (DFT). The crystal structure of the 4C6MQ compound has been brought to light by single-crystal x-ray diffraction (SCXRD) method which consists of two independent molecules (A and B) in the asymmetric unit with similar conformations. Both the isomer compounds are characterized spectroscopically by FTIR, FT-Raman, UV-Vis, and NMR spectrum and compared with DFT results. The geometries of the isomer compounds have been optimized by using DFT/B3LYP method with the 6-311G++(d,p) basis sets. From the optimized geometry of the compounds, geometric parameters (bond lengths, bond angles, and torsion angles); vibrational analysis; chemical shifts; and electronic absorption of the isomer compounds have been computed and compared with the experimental result. The detailed assignments of vibrational wave numbers have been prepared based on potential energy distribution (PED) which was carried out in the VEDA4 program. In addition, natural bonding orbital analysis, frontier molecular orbital, and molecular electrostatic potential have been explained theoretically. The in silico (absorption, distribution, metabolism, excretion and toxicity) studies were analyzed to identify the potential drug likeliness of the isomer compounds. The implications of the inhibitory activity of isomer compounds against DNA gyrase and lanosterol 14 α-demethylase enzyme by molecular docking are discussed. Further, the isomer compounds were screened for their antibacterial and antifungal activities.
- Murugavel,Sundramoorthy,Subashini,Pavan
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- Analysis of Cl...Cl and C-H...Cl intermolecular interactions involving chlorine in substituted 2-chloroquinoline derivatives
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Six crystal structures of substituted 2-chloroquinoline derivatives have been analysed to evaluate the role of Cl atom as a self recognizing unit resulting in the formation of Cl...Cl and C-H...Cl interactions to generate supramolecular assembly in the solid state. The features of Type I and Type II geometries associated with Cl...Cl interactions have been analysed to show directional preferences leading to differences in the packing motifs in these crystal structures. C-H...Cl interactions are generated exclusively in structures depicting Type II Cl...Cl interaction have been observed in these structures. Indian Academy of Sciences.
- Hathwar, Venkatesha R.,Mohana Roopan,Subashini,Nawaz Khan,Guru Row
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- A novel rearrangement of 3-arylisoxazol-5(4H)-ones: One-pot synthesis of new 2,4-dichloroquinoline-3-carbaldehydes
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Vilsmeier-Haack reaction, using a specific combination of phosphorus oxychloride and dimethylformamide, on 3-arylisoxazol-5(4H)ones 1 resulted in 2,4-dichloroquinoline-3-carbaldehydes 6 as the major products along with other minor products, through a novel rearrangement. Oxidation of 6 with alkaline potassium permanganate gave 2,4-dichloroquinoline-3-carboxylic acids 7. Decarboxylation of 6 and decarboxylation of 7 using aqueous sodium hydroxide yielded 2,4-dichloroquinolines 8. All the compounds were characterised by elemental and spectral analysis.
- Ashok,Sridevi,Umadevi
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- Synthesis and characterization of substituted 4-methoxy-1H-quinolin-2-ones
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An efficient method for the synthesis of various substituted 4- methoxy-1H-quinolin-2-ones from various substituted aniline with malonic acid, phosphorous oxychloride, sodium methoxide and glacial acetic acid under different conditions is described. The title compounds were synthesized from three steps; the first step involved the synthesis of substituted 2, 4-dichloro quinoline from aniline (substituted), with malonic acid and phosphorousoxychloride. In the second step, the substituted 2, 4 dichloro compounds was heated with freshly prepared methanolic sodium methoxide solution to give 2, 4-dimethoxy quinoline compounds, it was then refluxed with glacial acetic acid and hydrochloric acid to give the titled compounds in the final step. The purity of the synthesized compounds was confirmed by their C, H and N analysis and the structure was analyzed on the basics of Mass, FT-IR and 1H NMR.
- Ramasamy,Balasubramaniam,Mohan
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- An efficient click synthesis of chalcones derivatized with two 1-(2-quinolon-4-yl)-1,2,3-triazoles
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Chalcones derivatized with 1-(2-quinolonyl)-1,2,3-triazoles were synthesized by reaction of 4-azido-2-quinolones with 1-phenyl-3-(4-propargyloxyphenyl)prop-2-en-1-one, or by aldol reaction of 4-{[1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes with acetophenone. Whereas, chalcones bearing two 1-(2-quinolonyl)-1,2,3-triazoles were synthesized by reaction of 1,3-bis(4-propargyloxyphenyl)prop-2-en-1-one with 4-azido-2-quinolones, or by aldol condensation between 4-{4-[(4-acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl}quinolin-2(1H)-ones and 4-{[1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}benzaldehydes.
- Abdelhakem, Adel M.,Alshammari, Mohammed B.,Aly, Ashraf A.,Bakht, Md Afroz,Brown, Alan B.,El-Sheref, Essmat M.,Shawky, Ahmed M.
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p. 395 - 403
(2021/07/07)
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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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- Regioselective synthesis of novel 2-chloroquinoline derivatives of 1,4-dihydropyridines
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Highly regioselective reaction of some substituted 2,4-dichloroquinolines with symmetrical 1,4-dihydropyridines, leading to novel quinoline derivatives of DHPs, has been achieved in the presence of powdered K2CO 3, as a mild and efficient base, at moderate temperature. All the synthesized compounds were characterized by use of IR, NMR, and mass spectral data.
- Rajesh,Iniyavan,Sarveswari,Vijayakumar
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p. 1851 - 1866
(2014/05/06)
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- Ultrasound-promoted synthesis of novel 2-chloroquinolin-4-pyrimidine carboxylate derivatives as potential antibacterial agents
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Ultrasound-promoted reaction of substituted 2,4-dichloroquinolines (1) with ethyl 4-(3-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5- carboxylate (2) in the presence of K2CO3 as mild base at moderate temperatures leads
- Balaji,Rajesh,Kouser Ali, Shabana,Vijayakumar
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p. 1807 - 1815
(2013/06/05)
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- Ultrasound-promoted synthesis, biological evaluation and molecular docking of novel 7-(2-chloroquinolin-4-yloxy)-4-methyl-2H-chromen-2-one derivatives
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A series of quinoline-based coumarin derivatives have been synthesized by one pot dehydrochlorination of 2,4-dichloroquinolines (1a-g); 7-hydroxy-4-methyl-2H-chromen-2-one (2) under ultrasonic irradiation method with high regio selectivity. All the synthesized compounds were characterized through spectral data and screened against representative antibacterial and antioxidant activities. Some of the compounds are found to be equipotent or more potent than that of standard drugs. Molecular docking studies show that the binding energy value of the compounds is very less than that of standard chloroquine and amodiaquine drugs.
- Balaji,Rajesh,Priya,Iniyavan,Siva,Vijayakumar
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p. 3185 - 3192
(2013/07/19)
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- Synthesis and characterization of substituted 4-methoxy-1H-quinolin-2- thiones
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The synthesis of various substituted 4-methoxy-1H-quinolin-2-thiones from various substituted aniline with malonic acid, phosphorousoxychloride, sodium methoxide glacial acetic acid and thiourea under different conditions is described. All these substituted 4-methoxy-1H-quinolin-2-thiones were synthesized from four steps; the first step involved the synthesis of substituted 2,4-dichloro quinoline from aniline (substituted), with malonic acid and phosphorous-oxychloride. In the second step, the substituted 2,4-dichloro compound was heated with freshly prepared methanolic sodium methoxide solution to give 2,4-dimethoxy quinoline compounds, it was then refluxed with glacial acetic acid and hydrochloric acid to get the substituted 4-methoxy-1H-quinolin- 2-one. The final steps involves with an objective of introducing a chloro in the position 2 of the quinolone system, the substituted 4-methoxy-1H-quinolin-2-one was refluxed with distilled PoCl3 chloroform. The substituted 2-chloro-4-methoxy quinoline was then refluxed with thiourea and alcohol to get substituted 4-methoxy-1H-quinolin-2-thiones. The purity of the synthesized compound was judged by their C, H and N analysis and the structure was analyzed on the basics of mass, FT-IR and 1H NMR.
- Ramasamy,Balasubramaniam,Mohan
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experimental part
p. 4726 - 4728
(2012/09/07)
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- 4-thio substituted quinoline and naphthyridine compounds
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The present invention relates to 4-thio substituted quinoline and naphthyridine derivatives and processes for their preparation. The invention also related to methods for treating infection of Hepatitis C virus by administering a 4-thio substituted quinoline or naphthyridine derivative.
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Page/Page column 14
(2009/04/24)
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- 4-THIO SUBSTITUTED QUINOLINE AND NAPHTHYRIDINE COMPOUNDS
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The present invention relates to 4-thio substituted quinoline and naphthyridine derivatives and processes for their preparation. The invention also related to methods for treating infection of Hepatitis C virus by administering a 4-thio substituted quinoline or naphthyridine derivative.
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(2008/06/13)
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- Acetonitrile-mediated synthesis of 2,4-dichloroquinoline from 2-ethynylaniline and 2,4-dichloroquinazoline from anthranilonitrile
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2,4-Dichloroquinolines and 2,4-dichloroquinazolines were synthesized from 2-ethynylanilines and anthranilonitriles, respectively, using diphosgene in acetonitrile and heating at 130 °C or 150 °C for 12 hours. This reaction was applied to the synthesis of 4,6-dichloropyrazolo[3,4-d]pyrimidine (dichloro-9H-isopurine). The postulated mechanism is also described. Georg Thieme Verlag Stuttgart.
- Lee, Jae Hak,Lee, Byoung Se,Shin, Hyunik,Nam, Do Hyun,Chi, Dae Yoon
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- Quinolones used as MRS inhibitors and bactericides
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Compounds of formula (I) are inhibitors of the bacterial enzymeS aureusmethionyl tRNA synthetase and are of use in treating bacterial infections.
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- A convenient synthesis of 8,9,10,11-tetrahydrodibenzo[b,h] [1,6]naphthyridin-6(5H)ones
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Substituted 8,9,10,11-tetrahydrodibenzo[b,h][1,6]naphthyridin-6(5H)ones (5) have been synthesized by the condensation of 4-amino-3-formylquinolin-2(1H)ones (4) with cyclohexanone in presence of acetic acid and sulphuric acid. The precusors have been obtained by the animation of 4-chloro-3-formylquinolin-2(1H)ones (3).
- Arul Prakash,Rajendran
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p. 353 - 358
(2007/10/03)
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- 2,4-Dihalogenoquinolines. Synthesis, Orientation Effects and 1H and 13C NMR Spectral Studies
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Isomer ratios for the syntheses of 2,4-dichloroquinolines from meta-substituted and 3,4-disubstituted anilines are reported, a synthesis of 2,4-dibromoquinoline 1b is also described.The structures of certain bromination products 17 and 1f obtained from 4-hydroxy-2-quinolone have been revised.A thorough study of the 1H and 13C NMR spectra of a series of 2,4-dihalogenoquinolines is presented and the effects of the halogen substituents on JCH couplings are highlighted.
- Osborne, Alan G.,Buley, Jill M.,Clarke, Helen,Dakin, Rachel C. H.,Price, Paul I.
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p. 2747 - 2756
(2007/10/02)
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- Quinoline antifolate thymidylate synthase inhibitors: Variation of the C2- and C4-substituents
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Modifications to the bicyclic ring system of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(2-amino-3,4-dihydro-4-oxo-6- quinazolinyl)methyl]-N-prop-2-ynylamino]benzoyl]-L-glutamic acid (1, CB3717) have led to the synthesis of a series of quinol
- Warner,Barker,Jackman,Burrows,Roberts,Bishop,O'Connor,Hughes
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p. 2761 - 2768
(2007/10/02)
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