Azhar International Journal of Pharmaceutical and Medical Sciences
Six compounds were extracted from the ethyl acetate fraction of Chrysanthemum dante purple maxim.... more Six compounds were extracted from the ethyl acetate fraction of Chrysanthemum dante purple maxim. flowers for the first time, and identified as; luteolin (1), quercetin (2), apigenin 7-O-β-Dglucopyranoside (3), luteolin 7-O-β-D-glucopyranoside (4), rutin (5) and daucosterol (6). The structures of the extracted compounds had been established by comparison of their NMR and MS data with published ones. Free radical scavenging activity of flowers compound (1), total methanolic extract and fractions and confirmed that they had potent antioxidant activity even with lower concentrations, IC50 of all tested samples was temperately low between 0.3 and 0.6 mg/ml. All samples showed also potent cholesterol reduction ability. Concerning anti-inflammatory activity, the protection provided by compound (1), (luteolin), and butanol fraction were the most potent even with the lowest concentration. Further antiproliferative activity of all tested samples showed good anti-tumor activity even with low concentrations against human colorectal (HCT-116) and hepatic (HepG-2) cancer cells exceeding Doxorubicin and moderate antitumor activity against breast (MCF-7) cancer with no cytotoxic activity against BJ-1 human skin healthy cell-line. This could promote the use of C. dante purple flower extract for pharmacological and health purposes.
Novel naphthalene-heterocycle hybrids were synthesized via tandem reactions of 3-formylchromone w... more Novel naphthalene-heterocycle hybrids were synthesized via tandem reactions of 3-formylchromone with different nucleophilic reagents. Various hybrids revealed potent antitumor and anti-inflammatory as well as promising antituberculosis activities.
For anticancer cell line evaluation, a new sequence of pyrazolo [1-5a] pyrimidine and imidazo[1,2... more For anticancer cell line evaluation, a new sequence of pyrazolo [1-5a] pyrimidine and imidazo[1,2-b] pyrazole derivatives were synthesized. The reaction of 5-aminopyrazolo with appropriate functionalized enaminones derivatives and 2-bromoacetophenone to afford, respectively. In vitro tests were performed on the newly synthesized compounds against HepG-2 and MCF-7 cancer cells to assay their cytotoxicity. A few compounds showed promising activity as anticancer agents against MCF-7 cancer cell.
A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[g]quinazolines (1–17) were synthesized, cha... more A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[g]quinazolines (1–17) were synthesized, characterized, and evaluated in vitro for their antiangiogenesis VEGFR-2-targeting, antiproliferative, and antiapoptotic activities against breast MCF-7 and liver HepG2 cells. Flow cytometry was used to determine cancer-cell cycle distributions, and apoptosis was detected using annexin-V-FITC (V) and propidium iodide (PI) dyes. Fluorescence microscopy, in combination with Hoechst staining was used to detect DNA fragmentation. Most of the tested benzo[g]quinazolines demonstrated promising activity (IC50 = 8.8 ± 0.5–10.9 ± 0.9 μM) and (IC50 = 26.0 ± 2.5–40.4 ± 4.1 μM) against MCF-7 and HepG2, respectively. Doxorubicin was used as a reference drug. Compounds 13–15 showed the highest activity against both cancer cell lines. Differential effects were detected by cell-cycle analysis, indicating similarities in the actions of 13 and 14 against both MCF7 and HepG2, involving the targeting of G1 and...
Background: Thienopyrimidine, triazole and thiazolidinone derivatives have newly attracted attent... more Background: Thienopyrimidine, triazole and thiazolidinone derivatives have newly attracted attention due to their effective pharmacological activities. They show antioxidant, antitumor, antimicrobial, antiviral, anti-inflammatory and analgesic Objective: Synthesis of new ethyl 2-amino-4-isopropyl-5-methylthiophene-3-carboxylate (2) was used as starting material to produce 2-mercapto-methylthienopyrimidinone (3), (4) and 2-hydrazinyl-methylthienopyrimidinone (5), via high yields and evaluating anticancer activities. Method: A series of novel Schiff's bases (6-9) were produced after treatment of (5) with aldehydes. Triazolopyrimidinones (6a, 7a, 8a, 9a) were produced from cyclization of benzylidene (6-9) using Br2 / AcOH or dry pyridine /Ac2O. Thiazolidinones (6b, 7b, 8b, 9b) were synthesized from benzylidene (6-9) with mercaptoacetic acid. Results: All compounds were synthesized in good yields (55-85%) in a regularly actual system under the mild condition. The new compounds have ...
A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was sy... more A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was synthesized via a one-pot, three-multicomponent reaction of appropriate aldehydes, 1H-tetrazole-5-amine and 3-cyanoacetyl indole in catalytic triethylamine. The cytotoxic activity of the new synthesized tetrazolopyrimidine-6-carbonitrile compounds was investigated against HCT-116, MCF-7, MDA-MB-231, A549 human cancer cell lines and one human healthy normal cell line (RPE-1) using the MTT cytotoxicity assay. Compounds 4h, 4b, 4c, 4i and 4a showed potent anticancer activities against human colon cancer. Additionally, all the compounds showed potent anticancer activities on human lung cancer.
: A new series of thiazoles substituted on the chromene scaffold were prepared by facial approach... more : A new series of thiazoles substituted on the chromene scaffold were prepared by facial approaches starting from (E)-1-(2,3-Dihydrochromen-4-ylidene)thiosemicarbazide derivatives (2a,b), The thiosemicarbazides (2a,b) were reacted with a series of α-halo carbonyl compounds to give the corresponding rhodanine analogues and reacted also with C-acetyl-or C-ethoxy-N-hydrazothiosemicarbazidenoyl chlorides to afford the corresponding tri- and tetra-substituted hybrid hydrazinyl thiazole substituted chromenes. The newly synthesized compounds were screened for their in-vitro antimicrobial and antitumor activities. Two of the newly synthesized compounds revealed significant antimicrobial activities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeuroginosa, and Candida albicans. All of the tested compounds exhibited excellent anticancer activity against HCT116 (colorectal carcinoma) human cell line.
The sole, dual and multi-fermentations of fruit and vegetable peels (FVPs) were investigated in o... more The sole, dual and multi-fermentations of fruit and vegetable peels (FVPs) were investigated in order to balance nutrition hierarchy for maximizing hydrogen potential via Batch experiments. The highest volumetric hydrogen production of 2.55 ± 0.07 L/L and hydrogen content of 64.7 ± 3.7% were registered for multi-fermentation of M-PTBO (25% pea +25% tomato + 25% banana +25% orange). These values outperformed sole and dual fermentation. The multi-fermentation of FVPs provided sufficient nutrients and trace elements for anaerobes, where C/N and C/P ratios were at levels of 24.7 ± 0.2 and 113.2 ± 9.4, respectively. In specific, harmonizing of macro and micro-nutrients remarkably maximized activities of amylase, protease and lipase to 4.23 ± 0.42, 0.035 ± 0.002 and 0.31 ± 0.02 U/mL, respectively, as well as, substantially incremented counts of Clostridium and Enterobacter sp. up to 5.81 ± 0.23×105 and 2.17 ± 0.09×106 cfu/mL, respectively. Furthermore, multifermentation of M-PTBO achieved the maximum net energy gain and profit of 1.82 kJ/gfeedstock and 4.11 $/kgfeedstock, respectively. Nutrients balance significantly develops bacterial activity in terms of hydrogen productivity, anaerobes reproduction, enzyme activities and soluble metabolites. As a result, overall fermentation bioprocess performance was improved.
The aim of this study is to assess an innovative economic approach for the production of both fer... more The aim of this study is to assess an innovative economic approach for the production of both fermentative hydrogen and biochar from fruit and vegetable peels (FVPs) via fermentation/pyrolysis process. Firstly, in fermentation batches, multi-fermentation of FVPs positively affected the harvested hydrogen yield and COD reduction efficiency, which reached their maximal values of 3.9 ± 0.6 mmol/gCOD and 56.2 ± 4.6% at batch of 25% pea + 25% tomato + 25% banana + 25% orange (M4). Secondly, digestates produced from all batches were pyrolyzed at 500 °C for investigating the potential for biochar production. Based on the characteristics of the pyrolyzed digestate, biochar produced from S1 (spinach) exhibited the highest specific surface area, density, pore volume, biochar production yield, and pyrolysis profit of 28.43 ± 3.95 m2/g, 1.93 ± 0.18 g/cm3, 0.59 ± 0.08 cm3/g, 59.04 ± 2.36%, and 3.66 $/kgfeedstock, respectively. However, the maximum overall profit from both fermentation and pyrolysis processes was 5.21 $/kgfeedstock and was denoted for M4.
Iron overload is inevitable in patients who are transfusion dependent. In young children with tra... more Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion-dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants (N 5 64 their age ranged from 10 to 18 (median 12) months, 54.7% males; receiving 6 transfusions; serum ferittin (SF) >400 to < 1000 ng/mL were randomized to "early start deferiprone" (.ES-DFP) at a low dose (50 mg/kg/ day) or to "delay chelation" (DC), and remained in the study until their serum ferritin (SF) level reached 1000 lg/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months postrandomization, 100% of the subjects in DC group had achieved SF > 1000 mg/L and TSAT > 70% compared with none in the ES-DFP group. LPI level > 0.6 mM was observed in 97% vs. 40% of the DS and ES groups, respectively, (P < 0.001). The time to reach SF > 1000 mg/L was delayed by 6 months in the ES-DFP group (P < 0.001) without escalating DFP dose. No unexpected, serious, or severe adverse events were seen in the ES-DFP group.
Two new series of 4-styryl-7-oxycoumarin derivatives 3a-i and 4-styryl-7-oxycoumarin-8-Mannich ba... more Two new series of 4-styryl-7-oxycoumarin derivatives 3a-i and 4-styryl-7-oxycoumarin-8-Mannich bases 6a-r were designed and synthesized. Ten compounds were evaluated for their antioxidant activity in vitro against DPPH and in vivo against lipid peroxidation, superoxide dismutase (SOD), glutathione-s-transferase (GST) and catalase (CAT) activities. Molecular modeling study was performed to predict the mode of binding of the target compounds in the binding site. Although the tested compounds showed moderate to low dose dependent DPPH inhibition activities in vitro, most of them displayed remarkable antioxidant effects in vivo. Compounds 1, 6b, 3c and 6r displayed significant decrease in MDA, SOD and CAT enzyme levels in H2O2treated rats. Free binding energy was estimated by docking, MM-PBSA and MM-GBSA. Molecular dynamics simulation followed by MM-GBSA calculation was correlated to the antioxidant effect. Compound 1 illustrated the highest MM-GBSA value (-20.38) and the best antioxida...
Azhar International Journal of Pharmaceutical and Medical Sciences
Six compounds were extracted from the ethyl acetate fraction of Chrysanthemum dante purple maxim.... more Six compounds were extracted from the ethyl acetate fraction of Chrysanthemum dante purple maxim. flowers for the first time, and identified as; luteolin (1), quercetin (2), apigenin 7-O-β-Dglucopyranoside (3), luteolin 7-O-β-D-glucopyranoside (4), rutin (5) and daucosterol (6). The structures of the extracted compounds had been established by comparison of their NMR and MS data with published ones. Free radical scavenging activity of flowers compound (1), total methanolic extract and fractions and confirmed that they had potent antioxidant activity even with lower concentrations, IC50 of all tested samples was temperately low between 0.3 and 0.6 mg/ml. All samples showed also potent cholesterol reduction ability. Concerning anti-inflammatory activity, the protection provided by compound (1), (luteolin), and butanol fraction were the most potent even with the lowest concentration. Further antiproliferative activity of all tested samples showed good anti-tumor activity even with low concentrations against human colorectal (HCT-116) and hepatic (HepG-2) cancer cells exceeding Doxorubicin and moderate antitumor activity against breast (MCF-7) cancer with no cytotoxic activity against BJ-1 human skin healthy cell-line. This could promote the use of C. dante purple flower extract for pharmacological and health purposes.
Novel naphthalene-heterocycle hybrids were synthesized via tandem reactions of 3-formylchromone w... more Novel naphthalene-heterocycle hybrids were synthesized via tandem reactions of 3-formylchromone with different nucleophilic reagents. Various hybrids revealed potent antitumor and anti-inflammatory as well as promising antituberculosis activities.
For anticancer cell line evaluation, a new sequence of pyrazolo [1-5a] pyrimidine and imidazo[1,2... more For anticancer cell line evaluation, a new sequence of pyrazolo [1-5a] pyrimidine and imidazo[1,2-b] pyrazole derivatives were synthesized. The reaction of 5-aminopyrazolo with appropriate functionalized enaminones derivatives and 2-bromoacetophenone to afford, respectively. In vitro tests were performed on the newly synthesized compounds against HepG-2 and MCF-7 cancer cells to assay their cytotoxicity. A few compounds showed promising activity as anticancer agents against MCF-7 cancer cell.
A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[g]quinazolines (1–17) were synthesized, cha... more A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[g]quinazolines (1–17) were synthesized, characterized, and evaluated in vitro for their antiangiogenesis VEGFR-2-targeting, antiproliferative, and antiapoptotic activities against breast MCF-7 and liver HepG2 cells. Flow cytometry was used to determine cancer-cell cycle distributions, and apoptosis was detected using annexin-V-FITC (V) and propidium iodide (PI) dyes. Fluorescence microscopy, in combination with Hoechst staining was used to detect DNA fragmentation. Most of the tested benzo[g]quinazolines demonstrated promising activity (IC50 = 8.8 ± 0.5–10.9 ± 0.9 μM) and (IC50 = 26.0 ± 2.5–40.4 ± 4.1 μM) against MCF-7 and HepG2, respectively. Doxorubicin was used as a reference drug. Compounds 13–15 showed the highest activity against both cancer cell lines. Differential effects were detected by cell-cycle analysis, indicating similarities in the actions of 13 and 14 against both MCF7 and HepG2, involving the targeting of G1 and...
Background: Thienopyrimidine, triazole and thiazolidinone derivatives have newly attracted attent... more Background: Thienopyrimidine, triazole and thiazolidinone derivatives have newly attracted attention due to their effective pharmacological activities. They show antioxidant, antitumor, antimicrobial, antiviral, anti-inflammatory and analgesic Objective: Synthesis of new ethyl 2-amino-4-isopropyl-5-methylthiophene-3-carboxylate (2) was used as starting material to produce 2-mercapto-methylthienopyrimidinone (3), (4) and 2-hydrazinyl-methylthienopyrimidinone (5), via high yields and evaluating anticancer activities. Method: A series of novel Schiff's bases (6-9) were produced after treatment of (5) with aldehydes. Triazolopyrimidinones (6a, 7a, 8a, 9a) were produced from cyclization of benzylidene (6-9) using Br2 / AcOH or dry pyridine /Ac2O. Thiazolidinones (6b, 7b, 8b, 9b) were synthesized from benzylidene (6-9) with mercaptoacetic acid. Results: All compounds were synthesized in good yields (55-85%) in a regularly actual system under the mild condition. The new compounds have ...
A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was sy... more A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was synthesized via a one-pot, three-multicomponent reaction of appropriate aldehydes, 1H-tetrazole-5-amine and 3-cyanoacetyl indole in catalytic triethylamine. The cytotoxic activity of the new synthesized tetrazolopyrimidine-6-carbonitrile compounds was investigated against HCT-116, MCF-7, MDA-MB-231, A549 human cancer cell lines and one human healthy normal cell line (RPE-1) using the MTT cytotoxicity assay. Compounds 4h, 4b, 4c, 4i and 4a showed potent anticancer activities against human colon cancer. Additionally, all the compounds showed potent anticancer activities on human lung cancer.
: A new series of thiazoles substituted on the chromene scaffold were prepared by facial approach... more : A new series of thiazoles substituted on the chromene scaffold were prepared by facial approaches starting from (E)-1-(2,3-Dihydrochromen-4-ylidene)thiosemicarbazide derivatives (2a,b), The thiosemicarbazides (2a,b) were reacted with a series of α-halo carbonyl compounds to give the corresponding rhodanine analogues and reacted also with C-acetyl-or C-ethoxy-N-hydrazothiosemicarbazidenoyl chlorides to afford the corresponding tri- and tetra-substituted hybrid hydrazinyl thiazole substituted chromenes. The newly synthesized compounds were screened for their in-vitro antimicrobial and antitumor activities. Two of the newly synthesized compounds revealed significant antimicrobial activities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeuroginosa, and Candida albicans. All of the tested compounds exhibited excellent anticancer activity against HCT116 (colorectal carcinoma) human cell line.
The sole, dual and multi-fermentations of fruit and vegetable peels (FVPs) were investigated in o... more The sole, dual and multi-fermentations of fruit and vegetable peels (FVPs) were investigated in order to balance nutrition hierarchy for maximizing hydrogen potential via Batch experiments. The highest volumetric hydrogen production of 2.55 ± 0.07 L/L and hydrogen content of 64.7 ± 3.7% were registered for multi-fermentation of M-PTBO (25% pea +25% tomato + 25% banana +25% orange). These values outperformed sole and dual fermentation. The multi-fermentation of FVPs provided sufficient nutrients and trace elements for anaerobes, where C/N and C/P ratios were at levels of 24.7 ± 0.2 and 113.2 ± 9.4, respectively. In specific, harmonizing of macro and micro-nutrients remarkably maximized activities of amylase, protease and lipase to 4.23 ± 0.42, 0.035 ± 0.002 and 0.31 ± 0.02 U/mL, respectively, as well as, substantially incremented counts of Clostridium and Enterobacter sp. up to 5.81 ± 0.23×105 and 2.17 ± 0.09×106 cfu/mL, respectively. Furthermore, multifermentation of M-PTBO achieved the maximum net energy gain and profit of 1.82 kJ/gfeedstock and 4.11 $/kgfeedstock, respectively. Nutrients balance significantly develops bacterial activity in terms of hydrogen productivity, anaerobes reproduction, enzyme activities and soluble metabolites. As a result, overall fermentation bioprocess performance was improved.
The aim of this study is to assess an innovative economic approach for the production of both fer... more The aim of this study is to assess an innovative economic approach for the production of both fermentative hydrogen and biochar from fruit and vegetable peels (FVPs) via fermentation/pyrolysis process. Firstly, in fermentation batches, multi-fermentation of FVPs positively affected the harvested hydrogen yield and COD reduction efficiency, which reached their maximal values of 3.9 ± 0.6 mmol/gCOD and 56.2 ± 4.6% at batch of 25% pea + 25% tomato + 25% banana + 25% orange (M4). Secondly, digestates produced from all batches were pyrolyzed at 500 °C for investigating the potential for biochar production. Based on the characteristics of the pyrolyzed digestate, biochar produced from S1 (spinach) exhibited the highest specific surface area, density, pore volume, biochar production yield, and pyrolysis profit of 28.43 ± 3.95 m2/g, 1.93 ± 0.18 g/cm3, 0.59 ± 0.08 cm3/g, 59.04 ± 2.36%, and 3.66 $/kgfeedstock, respectively. However, the maximum overall profit from both fermentation and pyrolysis processes was 5.21 $/kgfeedstock and was denoted for M4.
Iron overload is inevitable in patients who are transfusion dependent. In young children with tra... more Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion-dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants (N 5 64 their age ranged from 10 to 18 (median 12) months, 54.7% males; receiving 6 transfusions; serum ferittin (SF) >400 to < 1000 ng/mL were randomized to "early start deferiprone" (.ES-DFP) at a low dose (50 mg/kg/ day) or to "delay chelation" (DC), and remained in the study until their serum ferritin (SF) level reached 1000 lg/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months postrandomization, 100% of the subjects in DC group had achieved SF > 1000 mg/L and TSAT > 70% compared with none in the ES-DFP group. LPI level > 0.6 mM was observed in 97% vs. 40% of the DS and ES groups, respectively, (P < 0.001). The time to reach SF > 1000 mg/L was delayed by 6 months in the ES-DFP group (P < 0.001) without escalating DFP dose. No unexpected, serious, or severe adverse events were seen in the ES-DFP group.
Two new series of 4-styryl-7-oxycoumarin derivatives 3a-i and 4-styryl-7-oxycoumarin-8-Mannich ba... more Two new series of 4-styryl-7-oxycoumarin derivatives 3a-i and 4-styryl-7-oxycoumarin-8-Mannich bases 6a-r were designed and synthesized. Ten compounds were evaluated for their antioxidant activity in vitro against DPPH and in vivo against lipid peroxidation, superoxide dismutase (SOD), glutathione-s-transferase (GST) and catalase (CAT) activities. Molecular modeling study was performed to predict the mode of binding of the target compounds in the binding site. Although the tested compounds showed moderate to low dose dependent DPPH inhibition activities in vitro, most of them displayed remarkable antioxidant effects in vivo. Compounds 1, 6b, 3c and 6r displayed significant decrease in MDA, SOD and CAT enzyme levels in H2O2treated rats. Free binding energy was estimated by docking, MM-PBSA and MM-GBSA. Molecular dynamics simulation followed by MM-GBSA calculation was correlated to the antioxidant effect. Compound 1 illustrated the highest MM-GBSA value (-20.38) and the best antioxida...
Uploads
Papers by Hanem Awad