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Research paper thumbnail of Synthesis, antitumour and antioxidant activities of novel α,β-unsaturated ketones and related heterocyclic analogues: EGFR inhibition and molecular modelling study

Journal of Enzyme Inhibition and Medicinal Chemistry, 2018

New a,b-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxaz... more New a,b-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxazoline 9; pyridine 10-11; and quinoline-4-carboxylic acid 12a,b derivatives were synthesized and evaluated for in vitro antitumour activity against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was investigated by the ability of these compounds to scavenge the 2,2 0-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS þ). Compounds 6a, 6b, 7, and 8b exhibited potent antitumour activities against all tested cell lines with [IC 50 ] ffi5.5-18.1 mM), in addition to significantly high ABTS þ scavenging activities. In vitro EGFR kinase assay for 6a, 6b, 7, and 8b as the most potent antitumour compounds showed that; compounds 6b, and 7 exhibited worthy EGFR inhibition activity with IC 50 values of 0.56 and 1.6 mM, respectively, while compounds 6a and 8b showed good inhibition activity with IC 50 values of 4.66 and 2.16 mM, respectively, compared with sorafenib reference drug (IC 50 ¼ 1.28 mM). Molecular modelling studies for compounds 6b, 7, and 8b were conducted to exhibit the binding mode towards EGFR kinase, which showed similar interaction with erlotinib.

Research paper thumbnail of Synthesis and pharmacological evaluation of novel fused thiophene derivatives as 5HT 2A receptor antagonists: Molecular modeling study

European Journal of Medicinal Chemistry, 2010

Novel derivatives of cyclopentathienopyrimidinediones 6, pyridothienopyrimidinediones 7, ethyl cy... more Novel derivatives of cyclopentathienopyrimidinediones 6, pyridothienopyrimidinediones 7, ethyl cycloheptathiophene-3-carboxylates 10, ethyl tetrahydrothienopyridine-3-carboxylates 11, tetrahydrocycloheptathienopyrimidin-4(3H)-ones 12, tetrahydrotriazolobenzothienopyrimidin-5(4H)-ones 17 and tetrahydro-5H-cycloheptathienopyrimidin-4(3H)-ones 21 have been synthesized and tested for their 5-HT 2A antagonist activity. Preliminary pharmacological studies showed that compounds 3-

Research paper thumbnail of Synthesis and anti-inflammatory activity of novel (substituted)benzylidene acetone oxime ether derivatives: Molecular modeling study

European Journal of Medicinal Chemistry, 2010

Herein, we report the design, synthesis, and pharmacological properties of a series of substitute... more Herein, we report the design, synthesis, and pharmacological properties of a series of substituted benzylidene acetone oxime ether derivatives from the corresponding oxime derivatives. All the newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenin-induced rat paw oedema model. Among the compounds examined, compounds 5b and 7a showed the highest activity, nearly equivalent to that of the standard drug diclofenac sodium. Hence, they were screened for their analgesic activities using acetic acid-induced writhing model in mice and also, their ulcerogenic effects were studied. Compound 7a was found to possess significant antiinflammatory and analgesic activities with negligible ulcerogenic effect. Docking study of the synthesized compound 7a into the active site of COX-1 and COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.

Research paper thumbnail of Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: Molecular docking study

European Journal of Medicinal Chemistry, 2010

Novel derivatives of quinazoline (1e27) have been synthesized and tested for their antitumor acti... more Novel derivatives of quinazoline (1e27) have been synthesized and tested for their antitumor activity against three tumor cell lines among these cell lines the human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. All tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC 50 range of 3.35e6.81 mg/ml. With regarding broad-spectrum activity compounds 5, 9, 15, 18 and 20 exploited potent antitumor against human liver cell line (HEPG2), human breast cell line (MCF-7) and human cervix cell line (HELA) with IC 50 range of 3.35e5.59 mg/ml. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors.

Research paper thumbnail of Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX2 inhibitors: Molecular docking study

Bioorganic & Medicinal Chemistry, 2011

New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesize... more New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC 50 value of 0.45 lM and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.

Research paper thumbnail of Synthesis, antitumour and antioxidant activities of novel α,β-unsaturated ketones and related heterocyclic analogues: EGFR inhibition and molecular modelling study

Journal of Enzyme Inhibition and Medicinal Chemistry, 2018

New a,b-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxaz... more New a,b-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxazoline 9; pyridine 10-11; and quinoline-4-carboxylic acid 12a,b derivatives were synthesized and evaluated for in vitro antitumour activity against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was investigated by the ability of these compounds to scavenge the 2,2 0-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS þ). Compounds 6a, 6b, 7, and 8b exhibited potent antitumour activities against all tested cell lines with [IC 50 ] ffi5.5-18.1 mM), in addition to significantly high ABTS þ scavenging activities. In vitro EGFR kinase assay for 6a, 6b, 7, and 8b as the most potent antitumour compounds showed that; compounds 6b, and 7 exhibited worthy EGFR inhibition activity with IC 50 values of 0.56 and 1.6 mM, respectively, while compounds 6a and 8b showed good inhibition activity with IC 50 values of 4.66 and 2.16 mM, respectively, compared with sorafenib reference drug (IC 50 ¼ 1.28 mM). Molecular modelling studies for compounds 6b, 7, and 8b were conducted to exhibit the binding mode towards EGFR kinase, which showed similar interaction with erlotinib.

Research paper thumbnail of Synthesis and pharmacological evaluation of novel fused thiophene derivatives as 5HT 2A receptor antagonists: Molecular modeling study

European Journal of Medicinal Chemistry, 2010

Novel derivatives of cyclopentathienopyrimidinediones 6, pyridothienopyrimidinediones 7, ethyl cy... more Novel derivatives of cyclopentathienopyrimidinediones 6, pyridothienopyrimidinediones 7, ethyl cycloheptathiophene-3-carboxylates 10, ethyl tetrahydrothienopyridine-3-carboxylates 11, tetrahydrocycloheptathienopyrimidin-4(3H)-ones 12, tetrahydrotriazolobenzothienopyrimidin-5(4H)-ones 17 and tetrahydro-5H-cycloheptathienopyrimidin-4(3H)-ones 21 have been synthesized and tested for their 5-HT 2A antagonist activity. Preliminary pharmacological studies showed that compounds 3-

Research paper thumbnail of Synthesis and anti-inflammatory activity of novel (substituted)benzylidene acetone oxime ether derivatives: Molecular modeling study

European Journal of Medicinal Chemistry, 2010

Herein, we report the design, synthesis, and pharmacological properties of a series of substitute... more Herein, we report the design, synthesis, and pharmacological properties of a series of substituted benzylidene acetone oxime ether derivatives from the corresponding oxime derivatives. All the newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenin-induced rat paw oedema model. Among the compounds examined, compounds 5b and 7a showed the highest activity, nearly equivalent to that of the standard drug diclofenac sodium. Hence, they were screened for their analgesic activities using acetic acid-induced writhing model in mice and also, their ulcerogenic effects were studied. Compound 7a was found to possess significant antiinflammatory and analgesic activities with negligible ulcerogenic effect. Docking study of the synthesized compound 7a into the active site of COX-1 and COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.

Research paper thumbnail of Design, synthesis and biological evaluation of novel quinazoline derivatives as potential antitumor agents: Molecular docking study

European Journal of Medicinal Chemistry, 2010

Novel derivatives of quinazoline (1e27) have been synthesized and tested for their antitumor acti... more Novel derivatives of quinazoline (1e27) have been synthesized and tested for their antitumor activity against three tumor cell lines among these cell lines the human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. All tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC 50 range of 3.35e6.81 mg/ml. With regarding broad-spectrum activity compounds 5, 9, 15, 18 and 20 exploited potent antitumor against human liver cell line (HEPG2), human breast cell line (MCF-7) and human cervix cell line (HELA) with IC 50 range of 3.35e5.59 mg/ml. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors.

Research paper thumbnail of Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX2 inhibitors: Molecular docking study

Bioorganic & Medicinal Chemistry, 2011

New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesize... more New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC 50 value of 0.45 lM and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.