484-27-5Relevant academic research and scientific papers
Synthesis of new furothiazolo pyrimido quinazolinones from visnagenone or khellinone and antimicrobial activity
Abu-Hashem, Ameen Ali
, (2018)
Substituted-6-methyl-1-thioxo-1,2-dihydro-3H-furo[3,2-g]pyrimido[1,6-a]quinazolin-3-ones (5a,b) were synthesized from condensation of visnagenone (2a) or khellinone (2b) with 6-amino-thiouracil (3) in dimethylformamide or refluxing of (4a) or (4b) in dimethylformamide. Hence, compounds (5a,b) were used as the starting materials for preparing many new heterocyclic compounds such as; furo[3,2-g]pyrimido[1,6-a]quinazoline (6a,b), furo[3,2-g]thiazolo[20,30:2,3] pyrimido[1,6-a]quinazolinone (7a,b), substituted-benzylidene-furo[3,2-g]thiazolo[20,30:2,3]pyrimido [1,6-a]quinazoline-3,5-dione (8a-f), 3-oxo-furo[3,2-g]pyrimido[1,6-a]quinazoline-pentane-2,4-dione (9a,b), 1-(pyrazole)-furo[3,2-g]pyrimido[1,6-a]quinazolinone (10a,b), 2-(oxo or thioxo)-pyrimidinefuro[ 3,2-g]pyrimido[1,6-a]quinazolinone (11a-d), 1-(methylthio)-furo[3,2-g]pyrimido[1,6-a] quinazolinone (12a,b), 1-(methyl-sulfonyl)-furo[3,2-g]pyrimido[1,6-a]quinazolinone (13a,b) and 6-methyl-1-((piperazine) or morpholino)-3H-furo[3,2-g]pyrimido[1,6-a]quinazolin-3-one (14a-d). The structures of the prepared compounds were elucidated on the basis of spectral data (IR, 1H-NMR, 13C-NMR, MS) and elemental analysis. Antimicrobial activity was evaluated for the synthesized compounds against Gram-positive, Gram-negative bacteria and fungi. The new compounds, furothiazolo pyrimido quinazolines 8a-f and 11a-d displayed results excellent for growth inhibition of bacteria and fungi.
Derivatives of benzo[b]furan. Part I. Conformational studies of khellinone and visnaginone
Ruiz, Tomas Pena,Drzewiecka, Aleksandra,Koziol, Anna E.,Gomez, Manuel Fernandez,Ostrowska, Kinga,Struga, Marta,Kossakowski, Jerzy
, p. 1573 - 1584 (2012)
The structural analysis of khellinone and visnaginone indicated the planarity of the benzo[b]furan ring system. The oxygen or carbon atoms of the substituents, -OH, -OCH3, and -C(=O)CH3, are nearly coplanar with the aromatic ring. The molecular conformation is stabilized by the intramolecular O-H..O hydrogen bond formed between the ortho-substituted hydroxyl and acetyl groups. The intermolecular contacts present in the crystal structure are the C-H..O and C-H..π interactions and the π..π stacking. The energy surface for the internal rotation about the Csp2-O/C bonds in the khellinone and visnaginone molecules has been explored by quantum-chemical calculations. The density functional theory (DFT) methods yielded three stable conformers of khellinone and two of visnaginone obtained by a rotation of the methoxy group about the C4sp2-OCH3 bond. The most stable conformation in the gas phase is consistent with the stereochemistry of the molecules adopted in the solid. The secondary minima conformers have energies higher by 0.3-1.8 kcal/mol. The energy of the intramolecular O-H..O interactions, present in the molecular structure of all stable conformers, is around 18 kcal/mol at the DFT level. A complete and reliable assignment of the bands in the IR and Raman spectra of both compounds has been performed.
Synthesis of new quinoxaline, pyrimidine, and pyrazole furochromone derivatives as cytotoxic agents
Abu-Hashem, Ameen A.,El-Shazly, Mohamed
, p. 1853 - 1863 (2017)
Abstract: A series of novel quinoxaline, pyrimidine, and pyrazole furochromone derivatives were synthesized for the first time. These derivatives were prepared under mild conditions using a stepwise efficient methodology. The developed protocol led to the synthesis of furochromone derivatives in moderate to good yields (60–75%). The structures of the prepared derivatives were identified using several spectroscopic techniques including IR, NMR, and mass spectrometry. The cytotoxic activity of the synthesized derivatives was evaluated using in vitro Ehrlich ascites assay. Pyrazolobenzofurans exhibited the most potent effect suggesting the importance of pyrazole nucleus for the cytotoxic activity. Graphical abstract: [Figure not available: see fulltext.].
Synthesis of potent antitumor and antiviral benzofuran derivatives
Galal, Shadia A.,Abd El-All, Amira S.,Abdallah, Mohamed M.,El-Diwani, Hoda I.
, p. 2420 - 2428 (2009)
A new series of potent antitumor and antiviral benzofuran derivatives was synthesized by the reaction of the furochromone-6-carboxaldehydes 1 and 2 with different heterocyclic amines to yield the benzofuran-5-carbonyl derivatives 4-11. The synthesized compounds 1, 3-11 were tested against twelve different human cancer cell lines and all of the compounds were more potent than the comparative standards. The HIV inhibitory activity of the tested compounds 1, 3-11 showed that they have higher potency than Atevirdine. Moreover, compound 6 was significantly potent with wider therapeutic index. The HIV-1 RT inhibitory activity showed that compounds 10, 11, 3 and 4 were notably potent but with lower therapeutic index than Atevirdine. The HCV NS3-4A protease inhibitor activity of the tested compounds revealed that they have weaker potency and less therapeutic index than VX-950, although compounds 1, 4, 9 and 6, respectively exhibited significant activity.
Design, synthesis and anticancer activity of furochromone and benzofuran derivatives targeting VEGFR-2 tyrosine kinase
Abdelhafez, Omaima M.,Ali, Hamed I.,Amin, Kamelia M.,Abdalla, Mohamed M.,Ahmed, Eman Y.
, p. 25312 - 25324 (2015)
In continuation of our work concerning the relation between the anticancer and anti-vascular endothelial growth factor receptor (anti-VEGFR-2) activity of some synthesized compounds, we hereby designed and prepared three new series of furochromone and benzofuran derivatives (carbonitriles, sulfonyl hydrazides and imides). The prepared compounds were evaluated for their in vitro VEGFR-2 inhibitory activity, their cytotoxicity on fifteen human cancer cell lines and their in vivo antiprostate cancer activity. The highest anti-VEGFR-2 activity was demonstrated by 6-acetyl-4-methoxy-7-methyl-5H-furo[3,2-g]chromen-5-one (3), which exhibited the same IC50 value as the reference drug sorafenib (2.00 × 10-3 μM). On the other hand, most of the synthesized compounds showed potent cytotoxicity against most of the tested cell lines, in particular, the carbonitrile series (4a,b and 5a,d) which exhibited the best activity with IC50 values ranging from 3.56 × 10-13 to 4.89 × 10-7 μM. Moreover, the imide series (15-17) showed the most significant in vivo antiprostate cancer activity. An in silico GOLD molecular docking study has been done to explore the binding mode of interaction of the furochromone and benzofuran derivatives to VEGFR-2 kinase, and to reveal the correlation between IC50 (μM) of the enzymatic inhibition of VEGFR-2 kinase and the GoldScore fitness for further therapeutic application. This journal is
Antitumor and multikinase inhibition activities of some synthesized coumarin and benzofuran derivatives
Abd Elmageed, Zakaria Y.,Abdelhafez, Omaima M.,Ahmed, Eman Y.,Ahmed, Yasmine H.,Ali, Hamed I.,El-Telbany, Rania Farag A.,Serry, Aya M.,Zaafar, Dalia
, (2022/03/17)
Two new series of coumarin and benzofuran derivatives were designed, synthesized, and assessed for their in vitro and in vivo antitumor activities against breast cancer. Compounds 8, 9, 14, 15, and 17 exhibited the best antiproliferative activities (IC50: 0.07?2.94 μM) against the MCF-7 cell line, compared with lapatinib (IC50: 4.69 μM). Compound 14, with the most potent cytotoxic activity against MCF-7 cells, was capable of enhancing preG1 apoptosis and triggering cell cycle arrest at the G2/M phase. The kinase inhibitory activity of compound 14 against a panel of 22 kinases was examined to reveal multikinase inhibition within ?39% to ?97%. Furthermore, compound 14 exhibited potent in vivo Ehrlich (mammary adenocarcinoma) tumor regression, positive caspase-3, and negative EGFR immunoreaction, and was capable of elevating the catalase level. The physicochemical properties and pharmacokinetic parameters of compound 14 were investigated in silico for its druglikeness.
Synthesis and antimicrobial activity of novel 1, 2, 4-triazolopyrimido-furo-quinazolinones from natural furochromones (Visnagenone and khellinone)
Abu-Hashem, Ameen Ali,Hussein, Hoda A. R.,Aly, Ahmed S.
, p. 707 - 723 (2021/04/02)
Background: Previous and recent scientific research has shown that triazolopyrimidine and furochromones have a wide range of pharmacological activities for the treatment of numerous diseases, including anticancer, antiviral, anti-depressant, anti-microbial, anti-inflammatory, and analgesic activities. Objective: Preparation of new drugs derived from a natural furochromones as (1-hydrazinyl or methylthio),-furopyrimidoquinazolinone, 1, 2, 4-triazolopyrimidofuroquinazolin-5-one, and quina-zoline-pyrimidofuro-quinazoline-8, 10-dione and the study of their biological activity as antimi-crobial agents. Method: A series of novel N’-furopyrimidoquinazoline-hydrazide; 1, 2, 4-triazolopyrimidofuro-quinazolin-5-one; furopyrimidoquinazolin-3-one and quinazoline-pyrimidofuroquinazoline-8, 10-dione derivatives were synthesized from substituted (methylthio)-furopyrimidoquinazolinone (3a-b) and 1-hydrazinyl-furopyrimido-quinazolinone (4a-b) as the starting material. Results: All compounds were synthesized in good yields (71-95%) in a gradually efficient system under mild condition and some of the procedures were used such as microwave oven. The new compounds have been confirmed by means of different spectroscopic methods such as IR, 1D and 2D-NMR techniques and mass spectrum. The in vitro antimicrobial activities were evaluated for the prepared compounds using many types of bacteria (Gram-positive and Gram-negative) and fungi. Conclusion: 1, 2, 4-triazolopyrimidofuroquinazolin-5-one derivatives (10a-f, 8a-b, 7a-b and 6a-d) showed the most efficient antimicrobial activities compared with the cefotaxime sodium and nys-tatin as standard drugs.
Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds
Abdelhafez, Omaima M.,Ahmed, Eman Y.,Abdel Latif, Nehad A.,Arafa, Reem K.,Abd Elmageed, Zakaria Y.,Ali, Hamed I.
, p. 1308 - 1319 (2019/02/24)
Two new series of furochromone and benzofuran derivatives were designed, synthesized and evaluated for their in vitro anticancer activity against MCF-7 and MDA231 breast cancer cell lines. Compounds 5, 6, 7, 9, 15a, 16, 17a and 18 exhibited the best antip
Metal-Free Activation of C(sp3)–H Bond, and a Practical and Rapid Synthesis of Privileged 1-Substituted 1,2,3,4-Tetrahydroisoquinolines
Choudhury, Santosh Kumar,Rout, Pragati,Parida, Bibhuti Bhusan,Florent, Jean-Claude,Johannes, Ludger,Phaomei, Ganngam,Bertounesque, Emmanuel,Rout, Laxmidhar
, p. 5275 - 5292 (2017/09/29)
The reaction of cotarnine and acyl/aryl ketones in “green” solvents provides an efficient approach to an array of privileged 1,2,3,4-tetrahydroisoquinolines in excellent yields by metal-free activation of C(sp3)–H bonds. This one-pot procedure takes place under base-free conditions at room temperature, and tolerates a wide range of functionalities. The reaction is highly chemoselective, can be performed on a multi-gram scale, and pure products are isolated by simple filtration without workup. Interestingly, the complementary two-step procedure from cotarnine halide salts gives the Mannich products in good yields. The scope was elaborated to 9-bromocotarnine salts to access a range of 9-bromonoscapine-derived analogues. The methodology has been developed considering the structural similarity of cotarnine derivatives to noscapinoids, which represent an emerging class of microtubule-modulating anticancer agents.
Design, synthesis and structure-activity relationship of novel semi-synthetic flavonoids as antiproliferative agents
Ragab,Yahya,El-Naa,Arafa
, p. 506 - 520 (2014/07/07)
Various flavonoid scaffold based derivatives viz furochalcones (3a-e, 6a-d and 9a-d), furoflavones (10a-d, 11a-d, 12a-d, 18a&b), flavones (21a-d), furoaurones (13a,b, 14a-d and 15a-d) and 7-styrylfurochromones (22a-d and 25a-e) were designed and synthesiz
