Papers by Ibrahim F . Nassar
Acta Crystallographica Section E-structure Reports Online, Aug 3, 2013
![Research paper thumbnail of A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-<i>d</i>]pyrimidine and pyrazole derivatives as anti-tumor agents](https://attachments.academia-assets.com/120994119/thumbnails/1.jpg)
Journal of Enzyme Inhibition and Medicinal Chemistry, Jul 28, 2014
An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined us... more An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide with (E)-ethyl 2-cyano-3ethoxyacrylate. The cyclocondensation reaction of this substrate and its hydrazide derivative with urea, thiourea, formamide, formic acid, D-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9-carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate analogues furnished a series of pyrazolo [3,4-d]pyrimidine, pyrazolo [3,4-d]oxazin-4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4-oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively. The structure of the compound 3 was supported by X-Ray crystallographic data. Orally administrated, one of each of the series of pyrazoles showed significant effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies.
Nucleosides, Nucleotides & Nucleic Acids, Mar 21, 2017
ABSTRACT The chalcone derivatives 3a,b were cyclized upon reaction with thiourea to give the pyra... more ABSTRACT The chalcone derivatives 3a,b were cyclized upon reaction with thiourea to give the pyrazolo[3,4-d]pyrimidine derivatives 5a,b. Condensation of 5a,b and their hydrazide derivatives 8a,b with cyclic and acyclic glucose gave the condensed S- and N-glycosides 7a,b and 9a,b, respectively. Reaction of 3b with ethyl cyanoacetate followed by reaction with cyclic glucose afforded a mixture of the O- and/or N-glycoside isomers 12 and 13, respectively. The pyrazolo[3,4-c]pyrazole derivative 14 was also obtained from the reaction of 3b with hydrazine hydrate. A number of the synthesized compounds were screened for their antitumor activity against three different tumor cell lines HEPG2 (liver), HCT116 (colon) and MCF-7 (breast) with a docking study against CDK2.
Future Medicinal Chemistry, Apr 26, 2023
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
General methods: All the solvents used were commercially purchased and distilled before use. Reac... more General methods: All the solvents used were commercially purchased and distilled before use. Reactions were monitored by thin-layer chromatography (TLC) on silica gel plates (60 F254), visualizing with ultraviolet light. Column chromatography was performed on silica gel (230-400 mesh) using distilled petroleum ether, ethyl acetate, dichloromethane, chloroform, and methanol. Infra red spectra (KBr) were recorded
Journal of Alloys and Compounds, 2009
Abstract Conducting polymer/NiCr-ferrospinel nanocomposites were synthesized by in situ polymeriz... more Abstract Conducting polymer/NiCr-ferrospinel nanocomposites were synthesized by in situ polymerization of aniline in the presence of NiCr 0.5 Fe 1.5 O 4 nanoparticles via a reverse microemulsion route. The structure, morphology and magnetic properties of products were characterized by powder X-ray diffraction (XRD), infrared spectra, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and magnetic measurements. Structure and morphology analysis indicated that the NiCr 0.5 Fe 1.5 O 4 particles with the crystallite size in the range of 12–18 nm were embedded in the polymer matrix. The magnetization under applied magnetic field for nanocomposites exhibited a clearly hysteretic behavior. The formation mechanism of nanocomposites was proposed as well.
Nanocomposite material based on Iron nanoparticles colloidal (Fe-NPC) and Purine were used throug... more Nanocomposite material based on Iron nanoparticles colloidal (Fe-NPC) and Purine were used through this work. (Fe-NPC) was biosynthesized and characterized by dynamic light scattering (DLS) and UV-visible spectroscopy. Fe-NPC was evaluated as synergistic inhibition with two purine inhibitors namely 1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one (PU1) and 6-[(1-methyl-4-nitro-5imidazolyl) sulfanyl] purine (PU2) on the corrosion of carbon steel in 0.5 mol dm-3 H 2 SO 4 solution by electrochemical techniques. The potentidynamic polarization curves indicated that PU1 and PU2 behave as a mixed-type inhibitor while in the presence of Fe-NPC and its mixture with PU1 and PU2 behave as a cathodic inhibitor. There is a synergism between purine inhibitors and the biosynthesis Fe-NPC, and the values of synergism parameter (S) are higher than unity.
Archiv der Pharmazie, 2011
New compounds of 2-aryl-4H-3,1-benzothiazine set were synthesized and tested for their antiprolif... more New compounds of 2-aryl-4H-3,1-benzothiazine set were synthesized and tested for their antiproliferative activity as part of our research in the antitumor field. The title compounds were obtained by the reaction of aryl-modified sulfinylbis((2,4-dihydroxyphenyl)methanethione) with 2aminobenzyl alcohols. The reaction proceeded through thiobenzanilide intermediates, which were converted to the 4H-3,1-benzothiazine fused ring by an endocyclization process. The structures of compounds were identified from elemental, IR, 1 H-NMR, 13 C-NMR, and MS spectra analyses. The cytotoxicity in vitro against four human cancer cell lines was determined. The antiproliferative properties of some compounds were more beneficial than cisplatin studied comparatively.
![Research paper thumbnail of Synthesis, biological evaluation, and in silico studies of new CDK2 inhibitors based on pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e] [1,2,4]triazolo[1,5-c]pyrimidine scaffold with apoptotic activity](https://attachments.academia-assets.com/88653780/thumbnails/1.jpg)
Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its ... more Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. Pyrazolo pyrimidine derivatives were well established for their antitumor activity via CDK2 inhibition. In this research, new series of pyrazolopyrimidine derivatives (4-15) was designed and synthesised as novel CDK2 inhibitors. The anti-proliferative activities against MCF-7, HCT-116, and HepG-2 were used to evaluate their anticancer activity as novel CDK2 inhibitors. Most of the compounds showed superior cytotoxic activity against MCF-7 and HCT-116 compared to Sorafenib. Only compounds 8, 14, and 15 showed potent activity against HepG-2. The CDK2/cyclin A2 enzyme inhibitory activity was tested for all synthesised compounds. Compound 15 showed the most significant inhibitory activity with IC 50 0.061 ± 0.003 mM. It exerted remarkable alteration in Pre G1 and S phase cell cycle progression and caused apoptosis in HCT cells. In addition, the normal cell line cytotoxicity for compound 15 was assigned revealing low cytotoxic results in normal cells rather than cancer cells. Molecular docking was achieved on the designed compounds and confirmed the two essential hydrogen binding with Leu83 in CDK2 active site. In silico ADMET studies and drug-likeness showed proper pharmacokinetic properties which helped in structure requirements prediction for the observed antitumor activity.
Universal Journal of Pharmaceutical Research
Background: In recent papers, it was found that 1,3,4-oxadiazole, 1,3,4-thiadiazoleand 1,2,4-tri... more Background: In recent papers, it was found that 1,3,4-oxadiazole, 1,3,4-thiadiazoleand 1,2,4-triazole pharmacophores are present in several drugs, tiodazosin and nesapidil (antihypertensive), raltegravir (antiretroviral), Furamizole, cefazolin and ceftezole (antibiotics), acetazolamide and methazolamide (carbonic anhydrase inhibitors), sulfamethizole (antibacterial), fluconazole, ravuconazole, voriconazole, itraconazole, posaconazole, and tebuconazole (antifungal). Methods: Thiosemicarbazide was reacted with ethyl p-substituted-phenyl glycinate; namely, ethyl p-tolylglycinate (1), ethyl p-methoxyphenylglycinate (2) or ethyl p-bromophenylglycinate (3), respectively to give compounds 4-6, which then kept with conc. H2SO4 overnight to yield 1,3,4-thiadiazol-2-amine derivatives 7-9. Compounds 10-18 were yielded by reaction of compounds 7-9 with D-sugars namely, D-galactose, D-glucose and/ or D-xylose in ethanol and catalytic amount of acetic acid. Compounds (10-18) were then acetylated...
Universal Journal of Pharmaceutical Research
Background: In recent papers, it was found that 1,3,4-oxadiazole, 1,3,4-thiadiazoleand 1,2,4-tri... more Background: In recent papers, it was found that 1,3,4-oxadiazole, 1,3,4-thiadiazoleand 1,2,4-triazole pharmacophores are present in several drugs, tiodazosin and nesapidil (antihypertensive), raltegravir (antiretroviral), Furamizole, cefazolin and ceftezole (antibiotics), acetazolamide and methazolamide (carbonic anhydrase inhibitors), sulfamethizole (antibacterial), fluconazole, ravuconazole, voriconazole, itraconazole, posaconazole, and tebuconazole (antifungal). Methods: Thiosemicarbazide was reacted with ethyl p-substituted-phenyl glycinate; namely, ethyl p-tolylglycinate (1), ethyl p-methoxyphenylglycinate (2) or ethyl p-bromophenylglycinate (3), respectively to give compounds 4-6, which then kept with conc. H2SO4 overnight to yield 1,3,4-thiadiazol-2-amine derivatives 7-9. Compounds 10-18 were yielded by reaction of compounds 7-9 with D-sugars namely, D-galactose, D-glucose and/ or D-xylose in ethanol and catalytic amount of acetic acid. Compounds (10-18) were then acetylated...
RSC Advances
A new set of pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffo... more A new set of pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffolds (4–13) as well as the thioglycoside derivatives (14, 15) were designed, and synthesized as novel CDK2 targeting compounds.
Russian Journal of Bioorganic Chemistry, 2020
Russian Journal of General Chemistry, 2021
A group of new substituted pyrimidine compounds, and their thiazolopyrimidines and 1,3,4-oxadiazo... more A group of new substituted pyrimidine compounds, and their thiazolopyrimidines and 1,3,4-oxadiazolyl acyclic sugar derivatives have been synthesized as potential anti-cancer candidates. Oxadiazolyl-pyrimidine hybrid compounds have been synthesized by the reaction of thioacetohydrazide derivative with carbon disulfide and heterocyclization of sugar hydrazones with acetic anhydride. The synthesized products have been studied for their anticancer activity against human liver carcinoma (HepG-2) and human normal retina pigmented epithelium (RPE-1). The synthesized sugar hydrazine of D-glucose, its 1,3,4-oxadiazole acyclic nucleoside and arylidine derivative demonstrate high selective anti-cancer activity against liver cell line without side effects on normal cells.
![Research paper thumbnail of Discovery of pyrazolo[3,4-d]pyrimidine and
pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine
derivatives as novel CDK2 inhibitors: synthesis,
biological and molecular modeling investigations†](https://attachments.academia-assets.com/86286837/thumbnails/1.jpg)
CDK2 inhibition is an appealing target for cancer treatment that targets tumor cells in a selecti... more CDK2 inhibition is an appealing target for cancer treatment that targets tumor cells in a selective manner. A new set of small molecules featuring the privileged pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffolds (4–13) as well as the thioglycoside derivatives (14, 15) were designed,and synthesized as novel CDK2 targeting compounds. The growth of the three examined cell lines was significantly inhibited by most of the prepared compounds. Results revealed that most of the
compounds showed superior cytotoxic activities against MCF-7 and HCT-116 with IC50 range (45–97 nM) and (6–99 nM), respectively, and moderate activity against HepG-2 with IC50 range of (48–90 nM)compared to sorafenib (IC50: 144, 176 and 19 nM, respectively). Of these compounds, 14 & 15 showedthe best cytotoxic activities against the three cell lines with IC50 values of 45, 6, and 48 nM and 46, 7,and 48 nM against MCF-7, HCT-116 and HepG-2, respectively. Enzymatic inhibitory activity againstCDK2/cyclin A2 was achieved for the most potent anti-proliferative compounds. Compounds 14, 13 and15 revealed the most significant inhibitory activity with IC50 values of 0.057 0.003, 0.081 0.004 and 0.119 0.007 mM, respectively compared to sorafenib (0.184 0.01 mM). Compound 14 displayed potent dual activity against the examined cell lines and CDK2, and was thus selected for further
investigations. It exerted a significance alteration in cell cycle progression, in addition to apoptosis induction within HCT cells. Molecular docking simulation of the designed compounds confirmed the good fit into the CDK2 active site through the essential hydrogen bonding with Leu83. In silico ADMET studies and drug-likeness studies using a Boiled Egg chart showed suitable pharmacokinetic properties which helped in structure requirement prediction for the observed antitumor activity.
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Papers by Ibrahim F . Nassar
compounds showed superior cytotoxic activities against MCF-7 and HCT-116 with IC50 range (45–97 nM) and (6–99 nM), respectively, and moderate activity against HepG-2 with IC50 range of (48–90 nM)compared to sorafenib (IC50: 144, 176 and 19 nM, respectively). Of these compounds, 14 & 15 showedthe best cytotoxic activities against the three cell lines with IC50 values of 45, 6, and 48 nM and 46, 7,and 48 nM against MCF-7, HCT-116 and HepG-2, respectively. Enzymatic inhibitory activity againstCDK2/cyclin A2 was achieved for the most potent anti-proliferative compounds. Compounds 14, 13 and15 revealed the most significant inhibitory activity with IC50 values of 0.057 0.003, 0.081 0.004 and 0.119 0.007 mM, respectively compared to sorafenib (0.184 0.01 mM). Compound 14 displayed potent dual activity against the examined cell lines and CDK2, and was thus selected for further
investigations. It exerted a significance alteration in cell cycle progression, in addition to apoptosis induction within HCT cells. Molecular docking simulation of the designed compounds confirmed the good fit into the CDK2 active site through the essential hydrogen bonding with Leu83. In silico ADMET studies and drug-likeness studies using a Boiled Egg chart showed suitable pharmacokinetic properties which helped in structure requirement prediction for the observed antitumor activity.
compounds showed superior cytotoxic activities against MCF-7 and HCT-116 with IC50 range (45–97 nM) and (6–99 nM), respectively, and moderate activity against HepG-2 with IC50 range of (48–90 nM)compared to sorafenib (IC50: 144, 176 and 19 nM, respectively). Of these compounds, 14 & 15 showedthe best cytotoxic activities against the three cell lines with IC50 values of 45, 6, and 48 nM and 46, 7,and 48 nM against MCF-7, HCT-116 and HepG-2, respectively. Enzymatic inhibitory activity againstCDK2/cyclin A2 was achieved for the most potent anti-proliferative compounds. Compounds 14, 13 and15 revealed the most significant inhibitory activity with IC50 values of 0.057 0.003, 0.081 0.004 and 0.119 0.007 mM, respectively compared to sorafenib (0.184 0.01 mM). Compound 14 displayed potent dual activity against the examined cell lines and CDK2, and was thus selected for further
investigations. It exerted a significance alteration in cell cycle progression, in addition to apoptosis induction within HCT cells. Molecular docking simulation of the designed compounds confirmed the good fit into the CDK2 active site through the essential hydrogen bonding with Leu83. In silico ADMET studies and drug-likeness studies using a Boiled Egg chart showed suitable pharmacokinetic properties which helped in structure requirement prediction for the observed antitumor activity.