Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Thei... more Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Their chemical structures were determined based on comprehensive 1D and 2D NMR spectroscopy. Their MIC was determined against 12 microorganisms. Their exerted cytotoxicity on the immortalized normal cells, hTERT-RPE1 was assessed by the sulforhodamine-B assay. The viral inhibitory effects of compounds against Newcastle disease virus (NDV) and H5N1 influenza virus IV were evaluated. Four in vitro antioxidant assays were performed in comparison with BHT and trolox and a weak activity was exhibited. Acovenoside A was with potent against H5N1-IV and NDV with IC50 ≤ 3.2 and ≤ 2.1 μg/ml and SI values of 93.75 and 95.23%, respectively, in comparison to ribavirin. Its CC50 record on Vero cells was > 400 and 200 μg/ml, respectively. Acobioside A was the most active compound against a broad range of microbes while Pseudomonas aeruginosa was the most sensitive. Its MIC (0.07 μg/ml) was 1/100-fold of...
Acovenoside A (Acov-A) and acobioside A (Acob-A) were isolated from Acokanthera oblongifolia. The... more Acovenoside A (Acov-A) and acobioside A (Acob-A) were isolated from Acokanthera oblongifolia. Their anticancer properties were explored regarding, antiproliferative and antiangiogenic activities. The study included screening phase against six cancer cell lines followed by mechanistic investigation against HepG2 cancer cell line. The sulforhodamine-B (SRB) was used to determine their growth inhibitory power. In the other hand, flow cytometry techniques were recorded the cell death type and cell cycle analysis. The clonogenic (colony formation) and wound healing assays, enzyme-linked immunosorbent assay (ELISA) and molecular docking, were performed to evaluate the antiangiogenesis capability. Both compounds were strongly, inhibited four cancer cell lines at GI50 less than 100 nM. The in vitro mechanistic investigation against HepG2 resulted in cell accumulations at G2M phase and induction of apoptosis upon treating cells separately, with 400 nM Acov-A and 200 nM Acob-A. Interestingly,...
Medicinal plants particularly with higher nutritional values are attracting the attention of both... more Medicinal plants particularly with higher nutritional values are attracting the attention of both the pharmacological and nutritional affairs. In the present study, we extracted the wheat germ oil with cold press, hexane as well as supercritical carbon dioxide (SC-CO2). All were chemically and biologically (antimicrobial) evaluated to investigate how far can the differential in fatty acid composition affect the biological properties. The most eminent result was recorded by SC-CO2 oil. It was the only among the extracted oils that possessed moderate antibacterial and strong antifungal activities.
During our exploring the anticancer activity of some medicinal plants and their major metabolites... more During our exploring the anticancer activity of some medicinal plants and their major metabolites, the aerial parts of the Egyptian Matricaria chamomilla (flowers and stems) were studied. GC–MS analysis of the organic soluble extracts of the flowers and stems fractions revealed the presence of 43 and 45 compounds, respectively. Individual chromatographic purification of the flowers and stems’ extracts afforded three major compounds. Structures of these compounds were identified by 1D- and 2D-NMR and HRESI-MS spectroscopic data as bisabolol oxide A (1) and (E)-tonghaosu (2) (as mixture of ratio 2:1) from the flowers extract, meanwhile apigenin-7-β-d-glucoside (3) from the stems fraction. Biologically, the chamomile extracts announced significant antiproliferative activities exceeded in potency by ∼1.5 fold in case of the stem, recording GI50 13.16 and 17.04 μg/mL against Caco-2 and MCF-7, respectively. Both fractions were approximately equipotent against the migration of the same cel...
The fungus, Mortierella polycephala is one of the most productive sources of anticancer bioactive... more The fungus, Mortierella polycephala is one of the most productive sources of anticancer bioactive compounds namely those of pigment nature. During our investigation of the produced bioactive metabolites by the terrestrial M. polycephala AM1 isolated from Egyptian poultry feather waste, two main azaphilonoid pigments, monascin (1) and monascinol (2) were obtained as major products; their structures were identified by 1D (1H&13C) and 2D (1H–1H COSY, HMBC) NMR and HRESI-MS spectroscopic data. Biologically, cytotoxic activities of these compounds were broadly studied compared with the fungal extract. To predict the biological target for the presumed antitumor activity, an in silico study was run toward three proteins, topoisomerase IIα, topoisomerase IIβ, and VEGFR2 kinase. Monascinol (2) was expected to be moderately active against VEGFR2 kinase without any anticipated inhibition toward topo II isoforms. The in vitro study confirmed the docked investigation consistently and introduced ...
A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach ... more A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach to construct new coumarin analogous (4a-f and 8a-e) was described. Further, new formyl (5a,d-f) and nitro (9a,d-f) coumarin derivatives were synthesized via C-N coupling reaction of various cyclic secondary amines and 4-chloro-3-(formyl-/nitro)coumarins (1a,c), respectively. The confirmed compounds were screened for their in vitro anti-proliferative activity against KB-3-1, A549 and PC3 human cancer cell lines using resazurin cellular-based assay. Among them, coumarin derivatives 4e and 8e displayed the best anti-cervical cancer potency (KB-3-1) with IC 50 values of 15.5 ± 3.54 and 21 ± 4.24 µM, respectively. Also, 4e showed the most promising cytotoxicity toward A549 with IC 50 value of 12.94 ± 1.51 µM. As well, 9d presented a more significant impact of potency against PC3 with IC 50 7.31 ± 0.48 µM. Moreover, 8d manifested selectivity against PC3 (IC 50 = 20.16 ± 0.07 µM), while 8e was selective toward KB-3-1 cell line (IC 50 = 21 ± 4.24 µM). Matching with docking profile, the enzymatic assay divulged that 8e is a dual potent single-digit nanomolar inhibitor of VEGFR-2 and EGFR with IC 50 values of 24.67 nM and 31.6 nM that were almost equipotent to sorafenib (31.08 nM) and erlotinib (26.79 nM), respectively.
Two naturally new cyclic urea and amide derivatives, [1,3]-diazepan-2-one (1) and (S)-1,4-diaza-c... more Two naturally new cyclic urea and amide derivatives, [1,3]-diazepan-2-one (1) and (S)-1,4-diaza-cyclododecane-2,3-dion (2), were isolated from the organic extract of the sponge Hemimycale aff arabica collected from the Red Sea. This was together with 4-acetamido-2,6-dibromo-4-hydroxy-1,1-dimethoxycyclohexa-2,5-diene (3), 2,4-bis(1-methyl-1-phenylethyl)-phenol (4), βsitosterol (5), bis-[2-ethyl]-hexyl-phthylester, triglyceride fatty acid ester, and linoleic acid. The chemical structures of compounds 1 and 2 were determined based on 1D and 2D Nuclear Magnetic Resonance (NMR) and HR-ESIMS. Compounds 1 and 2 revealed high potency as antiglycated agents. The molecular docking study of compounds 1 and 2 using α-glucosidase, αamylase, dipeptidyl peptidase-IV, and glycogen synthase kinase was performed to check their efficiency as hypoglycemic agents. Both the sponge extract and compound 1 showed no cytotoxicity vs. the RPE-1 as a model of normal cell line.
Chemical investigation of the organic extract of the marine soft coral Sarcophyton glaucum from R... more Chemical investigation of the organic extract of the marine soft coral Sarcophyton glaucum from Red Sea, Egypt, afforded two new hydroazulenes; calamusin J (1) and its hydroperoxide derivative calamusin K (2) in addition to eight known compounds. Structure of compounds 1-2 were confirmed by intensive NMR and mass spectrometry studies. The coral extract and the obtained compounds were examined against a set of diverse microorganisms. The in vitro anti-cancer properties were assessed against colon (Caco-2) and breast (MCF-7) cell lines together with their exerted cytotoxicity on the immortalized normal epithelium (hTERT-RPE1) cell type. The anti-angiogenic power was also highlighted through suppressing MCF-7 cell migration and the significant inactivation of VEGFR2 enzyme. Compounds 1,2 are the most potent angiogenic inhibitors (represented by 1.2-and 1.4-fold enzyme inactivation, respectively) relative to sorafenib. The polyhydroxy sterol; 5-3,6,11-trihydroxy-24-methyl-9,11-seco-5a-cholest-7-en-9-one (S4) inhibited effectively the growth of Caco-2 and MCF-7 with GI50 of 0.62 and 2.3 µM, respectively.
Objectives A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyr... more Objectives A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitrile ( 6a , b ), (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl) methanone ( 9 – 11 ), and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5- a ]pyridine-8-carbonitrile ( 14 – 16 ) derivatives were synthesized and evaluated for their antioxidant and antimicrobial activities; in addition, their quantitative structure–activity relationships and molecular docking were investigated. Methods The target compounds 6a , b were synthesized by the following method: reaction of 5,6-dimethyl-1H-benzoimidazole-2-carbohydrazide ( 2 ) with 4-(dimethyl amino)benzaldehyde or anthracene-9-carbaldehyde yielded Schiff’s bases 3a , b , which were reacted with ethyl cyanoacetate to yield 1H-pyrazole-4-carbonitriles 4a , b ; N -methylation of 4a , b afforded 5a , b , which reacted with 4-aminoantipyrine to give 6a , b . In addition, 5-benzoyl-1H-benzo[d]imidazole-2-carbohydrazide ...
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...
Applied biochemistry and biotechnology, Jan 12, 2018
Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluate... more Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluated and screened for their hydrolase activities. Most of the isolates were found to be prolific producers of hydrolytic enzymes. Only 11 isolates exhibited maximum cellular contents of lipids, rhamnolipids, and protein in the fungal isolates under the isolation numbers MERVA5, MERVA22, MERVA25, MERVA29, MERVA32, MERVA34, MERV36, MERVA39, MERVA42, MERVA43, and MERVA44. These isolate extracts exhibit the highest reducing activities against carbohydrate-metabolizing enzymes including α-amylase, α-glucosidase, β-glucosidase, β-glucuronidase, and tyrosinase. Consequently, based on morphological and cultural criteria, as well as sequence information and phylogenetic analysis, these isolates could be identified and designated as Penicillium brevicombactum MERVA5, Arthrinium arundinis MERVA22, Diaporthe rudis MERVA25, Aspergillus versicolor MERVA29, Auxarthron alboluteum MERVA32, Dothiorella sarme...
The publisher regrets that an incorrect version of Fig. 3B was used in the article entitled 'Kine... more The publisher regrets that an incorrect version of Fig. 3B was used in the article entitled 'Kinetics and Molecular Docking of Vasicine from Adhatoda vasica: an Acetylcholinesterase Inhibitor for Alzheimer's Disease'. The correct version is as follows: The publisher would like to apologise for any inconvenience caused.
Multidrug resistance (MDR) remains a burden in cancer chemotherapy. Several members of ATP-bindin... more Multidrug resistance (MDR) remains a burden in cancer chemotherapy. Several members of ATP-binding cassette (ABC transporters) are responsible for the efflux of anticancer drugs outside cells decreasing the drug's effective intracellular concentration. Therefore, extensive efforts have been conducted by researcher to circumvent the activity of these transporters to enhance the success of chemotherapy. In the present study, we questioned the role played by two microRNAs, namely miR-98 and miR-214 in controlling their bioinformatics' predicted ABC efflux transporter targets ABCC5 and ABCC10, in addition to ABCB1 and ABCC1 in doxorubicin-resistant HCC cells (HepG2/Dox). miRNA mimics and inhibitors transfection were utilized to explore the role of both candidate molecules in MDR in HepG2/Dox cells. QRT-PCR and western blotting were used for quantitative gene and protein analyses. The study revealed that miR-214 mimics significantly upregulated ABCC1 and ABCC5. While, miR-98 and miR-214 inhibitors significantly down regulated ABCC5 and ABCC10, respectively. These results introduced a possible negative role played by both miR-98 and miR-214 on drug sensitization. Moreover, these findings clarified that the predicted targets for miR-98 and miR-214 were not confirmed experimentally.
Abstract The alcoholic extract of Adhatoda vasica showed strong and reversible inhibition of the ... more Abstract The alcoholic extract of Adhatoda vasica showed strong and reversible inhibition of the enzyme acetyl cholinesterase (AChE) with an IC 50 = 294 μg/mL. Phytochemical study of the total alcoholic extract of A. vasica yielded four known compounds vasicine, vasicinone, vasicole and anisotine. Vasicine reversibly and competitively inhibited AChE with ki value 11.24 μM. On the other hand, rest of isolated alkaloids showed no/or weak inhibitory effect on AChE. Vasicine showed binding similarity to both galantamine and tacrine in the catalytic site. The obtained results support the multi-pharmacological properties of vasicine, which can be considered as a promising inhibitor for acetyl cholinesterase where it can be used directly or indirectly for the development of efficient anti-Alzheimer drug.
Bulletin of Faculty of Pharmacy, Cairo University, 2015
Elevation of acetylcholinesterase enzyme (AChE) has been reported to be implicated in the etiolog... more Elevation of acetylcholinesterase enzyme (AChE) has been reported to be implicated in the etiology of Alzheimer disease (AD). One of the encouraged strategies to fight AD is the plant-derived inhibitors. Amaryllidaceae species are enriched source of alkaloids. The inhibitory properties of roots and bulbs of Pancratium maritimum L. against AChE have been previously reported. In the present study, the flowers of the wild Egyptian P. maritimum were subjected to screening assays to evaluate its potency as inhibitor to AChE. Besides, its antioxidant and cytotoxic properties were also addressed. The acetylcholinesterase inhibitory properties of P. maritimum; total extract and its alkaloid mixture were examined using Ellman's assay. The direct antioxidant examination was carried out using DPPH assay whereas the indirect was monitored by the ability to protect Hepa1c1c7 cells against the induced cytotoxicity produced by tert-butyl hydroperoxide (TBHP). The cytotoxic effect of the total extract and crude alkaloid mixture was evaluated against the human liver hepatoma cell line (HepG2). P. maritimum flowers showed significant inhibitory activity against AChE. The potency of the alkaloid mixture, representing 5.0% of the flowers weight (IC 50 ; 22.02 ± 0.59 lg/ml) was about fourfold of its total extract (IC 50 ; 97.67 ± 4.06 lg/ml). The total extract was able to protect about 33.4% of Hepa1c1c7 against the induced intoxication that carried by TBHP rather than the alkaloid mixture. Weak antioxidant and cytotoxic activities were recorded by both examined samples. Flowers of the Egyptian P. maritimum L. could be an enriched source of AChE inhibitors.
Background Egyptians recognized the healing power of herbs and used them in their medicinal formu... more Background Egyptians recognized the healing power of herbs and used them in their medicinal formulations. Nowadays, “Attarin” drug shops and the public use mainly the Unani medicinal system for treatment of their health problems including improvement of memory and old age related diseases. Numerous medicinal plants have been described in old literature of Arabic traditional medicine for treatment of Alzheimer’s disease (AD) (or to strengthen memory). Methods In this study, some of these plants were evaluated against three different preliminary bioassays related to AD to explore the possible way of their bio-interaction. Twenty three selected plants were extracted with methanol and screened in vitro against acetylcholinesterase (AChE) and cycloxygenase-1 (COX-1) enzymes. In addition, anti-oxidant activity using DPPH was determined. Results Of the tested plant extracts; Adhatoda vasica and Peganum harmala showed inhibitory effect on AChE at IC50 294 μg/ml and 68 μg/ml respectively. Mo...
Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders t... more Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders the successes of most of current available chemotherapies. ATP-binding cassette (ABC) trasporter proteins have been shown to contribute to the majority of MDR in various types of malignancies. c-myc has recently been reported to participate, at least partly, in MDR to some types of cancers. This study aimed to test whether c-myc could play a role, solely or with coordination with other ABCs, in the resistance of HepG2 cells to doxorubicin (Dox). MDR has been induced in wild-type HepG2 and has been verified both on gene and protein levels. Various assays including efflux assays as well as siRNA targeting ABCB1 and c-myc have been employed to explore the role of both candidate molecules in MDR in HepG2. Results obtained, with regard to ABCB1 silencing on HepG2/Dox cells, have shown that ABCB1-deficient cells exhibited a significant reduction in ABCC1 expression as compared to ABCB1-sufficient cells. However, these cells did not show a significant reduction in other tested ABCs (ABCC5 and ABCC10) while c-myc silencing had no significant effect on any of the studied ABCs. Moreover, silencing of ABCB1 on HepG2 significantly increased fluorescent calcein retention in HepG2 cells as compared to the control cells while downregulation of c-myc did not have any effect on fluorescent calcein retention. Altogether, this work clearly demonstrates that c-myc has no role in MDR of HepG2 to Dox which has been shown to be ABCB1-mediated in a mechanism which might involve ABCC1.
Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Thei... more Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Their chemical structures were determined based on comprehensive 1D and 2D NMR spectroscopy. Their MIC was determined against 12 microorganisms. Their exerted cytotoxicity on the immortalized normal cells, hTERT-RPE1 was assessed by the sulforhodamine-B assay. The viral inhibitory effects of compounds against Newcastle disease virus (NDV) and H5N1 influenza virus IV were evaluated. Four in vitro antioxidant assays were performed in comparison with BHT and trolox and a weak activity was exhibited. Acovenoside A was with potent against H5N1-IV and NDV with IC50 ≤ 3.2 and ≤ 2.1 μg/ml and SI values of 93.75 and 95.23%, respectively, in comparison to ribavirin. Its CC50 record on Vero cells was > 400 and 200 μg/ml, respectively. Acobioside A was the most active compound against a broad range of microbes while Pseudomonas aeruginosa was the most sensitive. Its MIC (0.07 μg/ml) was 1/100-fold of...
Acovenoside A (Acov-A) and acobioside A (Acob-A) were isolated from Acokanthera oblongifolia. The... more Acovenoside A (Acov-A) and acobioside A (Acob-A) were isolated from Acokanthera oblongifolia. Their anticancer properties were explored regarding, antiproliferative and antiangiogenic activities. The study included screening phase against six cancer cell lines followed by mechanistic investigation against HepG2 cancer cell line. The sulforhodamine-B (SRB) was used to determine their growth inhibitory power. In the other hand, flow cytometry techniques were recorded the cell death type and cell cycle analysis. The clonogenic (colony formation) and wound healing assays, enzyme-linked immunosorbent assay (ELISA) and molecular docking, were performed to evaluate the antiangiogenesis capability. Both compounds were strongly, inhibited four cancer cell lines at GI50 less than 100 nM. The in vitro mechanistic investigation against HepG2 resulted in cell accumulations at G2M phase and induction of apoptosis upon treating cells separately, with 400 nM Acov-A and 200 nM Acob-A. Interestingly,...
Medicinal plants particularly with higher nutritional values are attracting the attention of both... more Medicinal plants particularly with higher nutritional values are attracting the attention of both the pharmacological and nutritional affairs. In the present study, we extracted the wheat germ oil with cold press, hexane as well as supercritical carbon dioxide (SC-CO2). All were chemically and biologically (antimicrobial) evaluated to investigate how far can the differential in fatty acid composition affect the biological properties. The most eminent result was recorded by SC-CO2 oil. It was the only among the extracted oils that possessed moderate antibacterial and strong antifungal activities.
During our exploring the anticancer activity of some medicinal plants and their major metabolites... more During our exploring the anticancer activity of some medicinal plants and their major metabolites, the aerial parts of the Egyptian Matricaria chamomilla (flowers and stems) were studied. GC–MS analysis of the organic soluble extracts of the flowers and stems fractions revealed the presence of 43 and 45 compounds, respectively. Individual chromatographic purification of the flowers and stems’ extracts afforded three major compounds. Structures of these compounds were identified by 1D- and 2D-NMR and HRESI-MS spectroscopic data as bisabolol oxide A (1) and (E)-tonghaosu (2) (as mixture of ratio 2:1) from the flowers extract, meanwhile apigenin-7-β-d-glucoside (3) from the stems fraction. Biologically, the chamomile extracts announced significant antiproliferative activities exceeded in potency by ∼1.5 fold in case of the stem, recording GI50 13.16 and 17.04 μg/mL against Caco-2 and MCF-7, respectively. Both fractions were approximately equipotent against the migration of the same cel...
The fungus, Mortierella polycephala is one of the most productive sources of anticancer bioactive... more The fungus, Mortierella polycephala is one of the most productive sources of anticancer bioactive compounds namely those of pigment nature. During our investigation of the produced bioactive metabolites by the terrestrial M. polycephala AM1 isolated from Egyptian poultry feather waste, two main azaphilonoid pigments, monascin (1) and monascinol (2) were obtained as major products; their structures were identified by 1D (1H&13C) and 2D (1H–1H COSY, HMBC) NMR and HRESI-MS spectroscopic data. Biologically, cytotoxic activities of these compounds were broadly studied compared with the fungal extract. To predict the biological target for the presumed antitumor activity, an in silico study was run toward three proteins, topoisomerase IIα, topoisomerase IIβ, and VEGFR2 kinase. Monascinol (2) was expected to be moderately active against VEGFR2 kinase without any anticipated inhibition toward topo II isoforms. The in vitro study confirmed the docked investigation consistently and introduced ...
A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach ... more A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach to construct new coumarin analogous (4a-f and 8a-e) was described. Further, new formyl (5a,d-f) and nitro (9a,d-f) coumarin derivatives were synthesized via C-N coupling reaction of various cyclic secondary amines and 4-chloro-3-(formyl-/nitro)coumarins (1a,c), respectively. The confirmed compounds were screened for their in vitro anti-proliferative activity against KB-3-1, A549 and PC3 human cancer cell lines using resazurin cellular-based assay. Among them, coumarin derivatives 4e and 8e displayed the best anti-cervical cancer potency (KB-3-1) with IC 50 values of 15.5 ± 3.54 and 21 ± 4.24 µM, respectively. Also, 4e showed the most promising cytotoxicity toward A549 with IC 50 value of 12.94 ± 1.51 µM. As well, 9d presented a more significant impact of potency against PC3 with IC 50 7.31 ± 0.48 µM. Moreover, 8d manifested selectivity against PC3 (IC 50 = 20.16 ± 0.07 µM), while 8e was selective toward KB-3-1 cell line (IC 50 = 21 ± 4.24 µM). Matching with docking profile, the enzymatic assay divulged that 8e is a dual potent single-digit nanomolar inhibitor of VEGFR-2 and EGFR with IC 50 values of 24.67 nM and 31.6 nM that were almost equipotent to sorafenib (31.08 nM) and erlotinib (26.79 nM), respectively.
Two naturally new cyclic urea and amide derivatives, [1,3]-diazepan-2-one (1) and (S)-1,4-diaza-c... more Two naturally new cyclic urea and amide derivatives, [1,3]-diazepan-2-one (1) and (S)-1,4-diaza-cyclododecane-2,3-dion (2), were isolated from the organic extract of the sponge Hemimycale aff arabica collected from the Red Sea. This was together with 4-acetamido-2,6-dibromo-4-hydroxy-1,1-dimethoxycyclohexa-2,5-diene (3), 2,4-bis(1-methyl-1-phenylethyl)-phenol (4), βsitosterol (5), bis-[2-ethyl]-hexyl-phthylester, triglyceride fatty acid ester, and linoleic acid. The chemical structures of compounds 1 and 2 were determined based on 1D and 2D Nuclear Magnetic Resonance (NMR) and HR-ESIMS. Compounds 1 and 2 revealed high potency as antiglycated agents. The molecular docking study of compounds 1 and 2 using α-glucosidase, αamylase, dipeptidyl peptidase-IV, and glycogen synthase kinase was performed to check their efficiency as hypoglycemic agents. Both the sponge extract and compound 1 showed no cytotoxicity vs. the RPE-1 as a model of normal cell line.
Chemical investigation of the organic extract of the marine soft coral Sarcophyton glaucum from R... more Chemical investigation of the organic extract of the marine soft coral Sarcophyton glaucum from Red Sea, Egypt, afforded two new hydroazulenes; calamusin J (1) and its hydroperoxide derivative calamusin K (2) in addition to eight known compounds. Structure of compounds 1-2 were confirmed by intensive NMR and mass spectrometry studies. The coral extract and the obtained compounds were examined against a set of diverse microorganisms. The in vitro anti-cancer properties were assessed against colon (Caco-2) and breast (MCF-7) cell lines together with their exerted cytotoxicity on the immortalized normal epithelium (hTERT-RPE1) cell type. The anti-angiogenic power was also highlighted through suppressing MCF-7 cell migration and the significant inactivation of VEGFR2 enzyme. Compounds 1,2 are the most potent angiogenic inhibitors (represented by 1.2-and 1.4-fold enzyme inactivation, respectively) relative to sorafenib. The polyhydroxy sterol; 5-3,6,11-trihydroxy-24-methyl-9,11-seco-5a-cholest-7-en-9-one (S4) inhibited effectively the growth of Caco-2 and MCF-7 with GI50 of 0.62 and 2.3 µM, respectively.
Objectives A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyr... more Objectives A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitrile ( 6a , b ), (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl) methanone ( 9 – 11 ), and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5- a ]pyridine-8-carbonitrile ( 14 – 16 ) derivatives were synthesized and evaluated for their antioxidant and antimicrobial activities; in addition, their quantitative structure–activity relationships and molecular docking were investigated. Methods The target compounds 6a , b were synthesized by the following method: reaction of 5,6-dimethyl-1H-benzoimidazole-2-carbohydrazide ( 2 ) with 4-(dimethyl amino)benzaldehyde or anthracene-9-carbaldehyde yielded Schiff’s bases 3a , b , which were reacted with ethyl cyanoacetate to yield 1H-pyrazole-4-carbonitriles 4a , b ; N -methylation of 4a , b afforded 5a , b , which reacted with 4-aminoantipyrine to give 6a , b . In addition, 5-benzoyl-1H-benzo[d]imidazole-2-carbohydrazide ...
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...
Applied biochemistry and biotechnology, Jan 12, 2018
Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluate... more Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios erectus, were evaluated and screened for their hydrolase activities. Most of the isolates were found to be prolific producers of hydrolytic enzymes. Only 11 isolates exhibited maximum cellular contents of lipids, rhamnolipids, and protein in the fungal isolates under the isolation numbers MERVA5, MERVA22, MERVA25, MERVA29, MERVA32, MERVA34, MERV36, MERVA39, MERVA42, MERVA43, and MERVA44. These isolate extracts exhibit the highest reducing activities against carbohydrate-metabolizing enzymes including α-amylase, α-glucosidase, β-glucosidase, β-glucuronidase, and tyrosinase. Consequently, based on morphological and cultural criteria, as well as sequence information and phylogenetic analysis, these isolates could be identified and designated as Penicillium brevicombactum MERVA5, Arthrinium arundinis MERVA22, Diaporthe rudis MERVA25, Aspergillus versicolor MERVA29, Auxarthron alboluteum MERVA32, Dothiorella sarme...
The publisher regrets that an incorrect version of Fig. 3B was used in the article entitled 'Kine... more The publisher regrets that an incorrect version of Fig. 3B was used in the article entitled 'Kinetics and Molecular Docking of Vasicine from Adhatoda vasica: an Acetylcholinesterase Inhibitor for Alzheimer's Disease'. The correct version is as follows: The publisher would like to apologise for any inconvenience caused.
Multidrug resistance (MDR) remains a burden in cancer chemotherapy. Several members of ATP-bindin... more Multidrug resistance (MDR) remains a burden in cancer chemotherapy. Several members of ATP-binding cassette (ABC transporters) are responsible for the efflux of anticancer drugs outside cells decreasing the drug's effective intracellular concentration. Therefore, extensive efforts have been conducted by researcher to circumvent the activity of these transporters to enhance the success of chemotherapy. In the present study, we questioned the role played by two microRNAs, namely miR-98 and miR-214 in controlling their bioinformatics' predicted ABC efflux transporter targets ABCC5 and ABCC10, in addition to ABCB1 and ABCC1 in doxorubicin-resistant HCC cells (HepG2/Dox). miRNA mimics and inhibitors transfection were utilized to explore the role of both candidate molecules in MDR in HepG2/Dox cells. QRT-PCR and western blotting were used for quantitative gene and protein analyses. The study revealed that miR-214 mimics significantly upregulated ABCC1 and ABCC5. While, miR-98 and miR-214 inhibitors significantly down regulated ABCC5 and ABCC10, respectively. These results introduced a possible negative role played by both miR-98 and miR-214 on drug sensitization. Moreover, these findings clarified that the predicted targets for miR-98 and miR-214 were not confirmed experimentally.
Abstract The alcoholic extract of Adhatoda vasica showed strong and reversible inhibition of the ... more Abstract The alcoholic extract of Adhatoda vasica showed strong and reversible inhibition of the enzyme acetyl cholinesterase (AChE) with an IC 50 = 294 μg/mL. Phytochemical study of the total alcoholic extract of A. vasica yielded four known compounds vasicine, vasicinone, vasicole and anisotine. Vasicine reversibly and competitively inhibited AChE with ki value 11.24 μM. On the other hand, rest of isolated alkaloids showed no/or weak inhibitory effect on AChE. Vasicine showed binding similarity to both galantamine and tacrine in the catalytic site. The obtained results support the multi-pharmacological properties of vasicine, which can be considered as a promising inhibitor for acetyl cholinesterase where it can be used directly or indirectly for the development of efficient anti-Alzheimer drug.
Bulletin of Faculty of Pharmacy, Cairo University, 2015
Elevation of acetylcholinesterase enzyme (AChE) has been reported to be implicated in the etiolog... more Elevation of acetylcholinesterase enzyme (AChE) has been reported to be implicated in the etiology of Alzheimer disease (AD). One of the encouraged strategies to fight AD is the plant-derived inhibitors. Amaryllidaceae species are enriched source of alkaloids. The inhibitory properties of roots and bulbs of Pancratium maritimum L. against AChE have been previously reported. In the present study, the flowers of the wild Egyptian P. maritimum were subjected to screening assays to evaluate its potency as inhibitor to AChE. Besides, its antioxidant and cytotoxic properties were also addressed. The acetylcholinesterase inhibitory properties of P. maritimum; total extract and its alkaloid mixture were examined using Ellman's assay. The direct antioxidant examination was carried out using DPPH assay whereas the indirect was monitored by the ability to protect Hepa1c1c7 cells against the induced cytotoxicity produced by tert-butyl hydroperoxide (TBHP). The cytotoxic effect of the total extract and crude alkaloid mixture was evaluated against the human liver hepatoma cell line (HepG2). P. maritimum flowers showed significant inhibitory activity against AChE. The potency of the alkaloid mixture, representing 5.0% of the flowers weight (IC 50 ; 22.02 ± 0.59 lg/ml) was about fourfold of its total extract (IC 50 ; 97.67 ± 4.06 lg/ml). The total extract was able to protect about 33.4% of Hepa1c1c7 against the induced intoxication that carried by TBHP rather than the alkaloid mixture. Weak antioxidant and cytotoxic activities were recorded by both examined samples. Flowers of the Egyptian P. maritimum L. could be an enriched source of AChE inhibitors.
Background Egyptians recognized the healing power of herbs and used them in their medicinal formu... more Background Egyptians recognized the healing power of herbs and used them in their medicinal formulations. Nowadays, “Attarin” drug shops and the public use mainly the Unani medicinal system for treatment of their health problems including improvement of memory and old age related diseases. Numerous medicinal plants have been described in old literature of Arabic traditional medicine for treatment of Alzheimer’s disease (AD) (or to strengthen memory). Methods In this study, some of these plants were evaluated against three different preliminary bioassays related to AD to explore the possible way of their bio-interaction. Twenty three selected plants were extracted with methanol and screened in vitro against acetylcholinesterase (AChE) and cycloxygenase-1 (COX-1) enzymes. In addition, anti-oxidant activity using DPPH was determined. Results Of the tested plant extracts; Adhatoda vasica and Peganum harmala showed inhibitory effect on AChE at IC50 294 μg/ml and 68 μg/ml respectively. Mo...
Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders t... more Multidrug resistance (MDR) in various kinds of cancers represents a true obstacle which hinders the successes of most of current available chemotherapies. ATP-binding cassette (ABC) trasporter proteins have been shown to contribute to the majority of MDR in various types of malignancies. c-myc has recently been reported to participate, at least partly, in MDR to some types of cancers. This study aimed to test whether c-myc could play a role, solely or with coordination with other ABCs, in the resistance of HepG2 cells to doxorubicin (Dox). MDR has been induced in wild-type HepG2 and has been verified both on gene and protein levels. Various assays including efflux assays as well as siRNA targeting ABCB1 and c-myc have been employed to explore the role of both candidate molecules in MDR in HepG2. Results obtained, with regard to ABCB1 silencing on HepG2/Dox cells, have shown that ABCB1-deficient cells exhibited a significant reduction in ABCC1 expression as compared to ABCB1-sufficient cells. However, these cells did not show a significant reduction in other tested ABCs (ABCC5 and ABCC10) while c-myc silencing had no significant effect on any of the studied ABCs. Moreover, silencing of ABCB1 on HepG2 significantly increased fluorescent calcein retention in HepG2 cells as compared to the control cells while downregulation of c-myc did not have any effect on fluorescent calcein retention. Altogether, this work clearly demonstrates that c-myc has no role in MDR of HepG2 to Dox which has been shown to be ABCB1-mediated in a mechanism which might involve ABCC1.
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