28 results on '"Mohamed, A. S. A."'
Search Results
2. Combination and tricombination therapy to destabilize the structural integrity of COVID-19 by some bioactive compounds with antiviral drugs: insights from molecular docking study
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El-Mageed, H. R. Abd, Abdelrheem, Doaa A., Ahmed, Shimaa A., Rahman, Aziz A., Elsayed, Khaled N. M., Ahmed, Sayed A., EL-Bassuony, Ashraf A., and Mohamed, Hussein S.
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- 2021
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3. Destabilizing the structural integrity of COVID-19 by caulerpin and its derivatives along with some antiviral drugs: An in silico approaches for a combination therapy
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Ahmed, Shimaa A., Abdelrheem, Doaa A., El-Mageed, H. R. Abd, Mohamed, Hussein S., Rahman, Aziz A., Elsayed, Khaled N. M., and Ahmed, Sayed A.
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- 2020
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4. Bioactive fluorenes. Part III: 2,7-dichloro-9H-fluorene-based thiazolidinone and azetidinone analogues as anticancer and antimicrobial against multidrug resistant strains agents
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Hussein, Essam M., Alsantali, Reem I., Morad, Moataz, Obaid, Rami J., Altass, Hatem M., Sayqal, Ali, Abourehab, Mohamed A. S., Elkhawaga, Amal A., Aboraia, Ahmed S. M., and Ahmed, Saleh A.
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- 2020
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5. Design, synthesis, and antitumor efficacy of novel 5-deazaflavin derivatives backed by kinase screening, docking, and ADME studies.
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Bedewy, Walaa A., Mohamed, Mosaad S., Abdelhameed, Ahmed M., Elsawy, Mohamed A., Al-Muhur, Mohammed, Ashida, Noriyuki, Abdalla, Ashraf N, Elwaie, Tamer A., Nagamatsu, Tomohisa, and Ali, Hamed I.
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HELA cells , *CYTOTOXINS , *CELL lines , *ANTINEOPLASTIC agents , *MOIETIES (Chemistry) - Abstract
Novel 5-deazaflavins were designed as potential anticancer candidates. Compounds 4j, 4k, 5b, 5i, and 9f demonstrated high cytotoxicity against MCF-7 cell line with IC50 of 0.5–190nM. Compounds 8c and 9g showed preferential activity against Hela cells (IC50: 1.69 and 1.52 μM respectively). However, compound 5d showed notable potency against MCF-7 and Hela cell lines of 0.1 nM and 1.26 μM respectively. Kinase profiling for 4e showed the highest inhibition against a 20 kinase panel. Additionally, ADME prediction studies exhibited that compounds 4j, 5d, 5f, and 9f have drug-likeness criteria to be considered promising antitumor agents deserving of further investigation. SAR study showed that substitutions with 2-benzylidene hydra zino have a better fitting into PTK with enhanced antiproliferative potency. Noteworthy, the incorporation of hydrazino or ethanolamine moieties at position 2 along with small alkyl or phenyl at N-10, respectively revealed an extraordinary potency against MCF-7 cells with IC50 values in the nanomolar range. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Novel benzo chromene derivatives: design, synthesis, molecular docking, cell cycle arrest, and apoptosis induction in human acute myeloid leukemia HL-60 cells.
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Abd El-Hameed, Rania H., Mohamed, Mosaad S., Awad, Samir M., Hassan, Bardes B., Khodair, Marwa Abd El-Fattah, and Mansour, Yara E.
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ACUTE myeloid leukemia , *CELL cycle , *MOLECULAR docking , *MOLECULES , *APOPTOSIS - Abstract
A series of benzo[h]chromenes, benzo[f]chromenes, and benzo[h]chromeno[2,3-d]pyrimidines were prepared. All the newly synthesised compounds were selected by National Cancer Institute for single-dose testing against 60 cell lines. Benzo[h]chromenes 5a and 6a showed promising anti-cancer activity and selected for the five-dose testing. Compounds 5a and 6a suppressed cell growth in HL-60 by the induction of cell cycle arrest, which was confirmed using flow cytometry and Annexin V-FITC/PI assays showed at the G1/S phase by regulating the expression of CDK-2/CyclinD1, triggering cell apoptosis by activating both the extrinsic (Fas/Caspase 8) and intrinsic (Bcl-2/Caspase 3) apoptosis pathways, which were determined by the western blot. Benzo[h]chromenes 5a and 6a decreased the protein expression levels of Bcl-2, CDK-2, and CyclinD1 and increased the expression of caspase 3, caspase 8, and Fas. In silico molecular analysis of compounds 5a and 6a in CDK-2 and Bcl-2 was performed. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Geigeria Alata- A Potential Source for Anti-Alzheimer's Constituents: In Vitro And Computational Investigations.
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Osman, Wadah, Maaz, Mohamed A., Ali, Amna, Fadul, Eltayeb, Arbab, Ahmed H., Al-Nour, Mosab Yahya, Ashour, Ahmed, Sherif, Asmaa E., Abulkhair, Hamada S., Ibrahim, Sabrin R. M., Ghazawi, Kholoud F., Mohamed, Gamal A., and Mohamed, Mona S.
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ALZHEIMER'S disease ,TANNINS ,ACETYLCHOLINESTERASE inhibitors ,DEGENERATION (Pathology) ,ETHYL acetate ,FLAVONOIDS ,PLANT extracts - Abstract
Antioxidants and acetylcholinesterase inhibitors play a key role in the prevention and management of degenerative disorders including Alzheimer's disease in particular. Identifying new anticholinesterases from natural sources may contribute to combating this class of diseases. The present study aimed to evaluate the potential anti-Alzheimer's activity of Geigeria alata (DC), a plant used in Sudanese folkloric medicine. Accordingly, the whole DC plant extract including twenty phytoconstituents of phenolic, flavonoid, and tannin types was evaluated in vitro as antioxidants and acetylcholinesterase inhibitors. Also, their pharmacokinetics, drug likeliness, and toxicity profiles were assessed. Additionally, the virtual binding of the plant's phytoconstituents with the cholinesterase target was investigated by docking against two AChE X-ray crystallographic structures. The best effective DPPH radical scavenging activity was demonstrated by both ethyl acetate and n-butanol fractions with percentages of inhibition of 91±0.02% and 90±0.02% (IC50 22±0.01 and 66±0.02 µg/mL), respectively. The ethyl acetate fraction showed statistically significant and the highest AChE inhibitory activity (78% inhibition, IC50 0.246±0.02mg/mL). Furthermore, the ethyl acetate fraction exhibited the highest total phenolic, flavonoid, and tannin values. Among identified compounds, quercetin and hispidulin showed promising in silico anti-AChE activity and hence merit further studies for the isolation and characterization of these active constituents. [ABSTRACT FROM AUTHOR]
- Published
- 2023
8. Pharmacokinetics and molecular docking of novel antineoplastic sesquiterpene lactone from Tarchonanthus camphoratus L: an in silico approaches.
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Shantier, Shaza W., Ismail, Esraa M. O., Mohamed, Mona S., and Osman, Wadah
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MOLECULAR docking ,DRUG discovery ,PHARMACOKINETICS ,NATURAL products ,BINDING energy - Abstract
Natural products are important in drug discovery because they provide structural clues for the creation of novel therapeutic treatments for a variety of ailments. The present study aims to focus on the in silico assessment of the therapeutic potential of phytochemical compounds isolated from Tarchonanthuscamphoratus L. The physicochemical and pharmacokinetic parameters of the three identified compounds were predicted using various integrated web-based tools. Following that, the PharmMapper web server was used to undertake structural-based virtual screening for the probable targets. Based on the findings, molecular docking was then used to investigate the binding interactions between the most promising lead and the targets indicated by the PharmMapper server. The obtained results revealed that the hydrogen bonds and total polar surface area for all compounds were within the limit range stated for Lipinski's rule of five and subsequently easily transported. However, only trifloculoside was found to be soluble (Log P = 2.3), permeable with no violation. Trifloculoside was suggested as potential antineoplastic agent based on its activity, safety, and binding energy to the target (− 6.8 kcal/mol). The obtained molecular dynamic simulation results were further supported the stability and flexibility of the complex. These findings suggest trifloculoside could be used as a starting point for future drug development initiatives in chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Utility of Pyrimidine Thione Derivatives in the Synthesis of Biologically Active Heterocyclic Compounds.
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Zaki, Yasser H., El-Gendey, Marwa S., Fouad, Sawsan A., Mohamed, Hussein S., and Amer, Hamada H.
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BIOACTIVE compounds ,PYRIMIDINE derivatives ,PYRIMIDINES ,SALMONELLA typhimurium ,MOLECULAR docking ,CARRIER proteins - Abstract
A new series of thieno[2,3-b]pyridine-2-carbohydrazide, 2,3 dihydropyrido[3′,2′:4,5]-thieno[3,2-d]pyrimidin-4(1H)-one, thieno[2,3-b]pyridin-2 yl)(3,5-substituted-1H-pyrazol-1-yl)methanone, tetrazolopyrimidine, and triazolopyrimdine derivatives have been synthesized. Molecular docking studies were performed on the most active compounds against the aspartic protease from Candida albicnas (1ZAP) and gram-negative (Salmonella typhimurium) binding protein (3ZQB) revealed the potential binding mode of the ligands to the site of the appropriate targets. To determine the direction of the reaction, compounds (19a) and (20a) were subjected to a computational study. Computational investigations are in complete agreement with experimental findings. Moreover, the selected newly synthesized products were evaluated for their antimicrobial activity. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Synthesis of 1,3,4-Thiadiazole Derivatives Using Hydrazonoyl Bromide: Molecular Docking and Computational Studies.
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Zaki, Yasser H., Abdelhamid, Abdou O., Sayed, Abdelwahed R., and Mohamed, Hussein S.
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MOLECULAR docking ,THIADIAZOLES ,BROMIDES ,STRUCTURAL dynamics ,HETEROCYCLIC compounds ,QUANTUM chemistry - Abstract
Alkyl phenylcarbamodithioates were reacted with hydrazonoyl bromide 1a, b in ethanol containing a catalytic amount of triethylamine solution to afford and 1,3,4-thiadiazole derevatives 5a, b, respectively. In the same manner, alkyl hydrazinecarbodithioate (6–10)a, b were reacted with the appropriate hydrazonoyl bromide (1a, b) in ethanol containing a catalytic amount of triethylamine solution to afford 1,3,4-thiadiazole derivatives (13–17), respectively. Moreover, hydrazonoyl bromide 1a or 1b was reacted with 5-phenyl-1,3,4-oxadiazole-2-thione 22A in refluxing chloroform containing triethylamine to give 1,3,4-thiadiazole derivatives 21a and b, respectively. Elemental analysis, spectral data, and an alternative synthetic route were used to confirm the structures of all the newly synthesized heterocyclic compounds. AutoDock was used to screen possible drugs. To screen potential medications, AutoDock was utilized. The antiviral medications chloroquine, hydroxychloroquine, and Lopinavir, as well as their synthesized components, were all tested. Confirmation comes from molecular docking and computational investigations. The results of a detailed exploration of the structural characterization of 5b and 13b using quantum chemistry methods calculated using the DFT (B3LYP) method with a 6-31 + g (d, p) basis set are presented in the computational study. The goal of this study was to investigate the molecular dynamics and structural characteristics that regulate chemical behavior, as well as to compare theoretical predictions with experimental results. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Bioguided isolation of potential antitumor agents from the aerial parts of cultivated cardoon (Cynara cardunculus var. altilis).
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Hamza, Rasha A., Mostafa, Islam, Mohamed, Yasmin S., Dora, Gamal A., Ateya, Abdel-Monem, Abdelaal, Mahmoud, Fantoukh, Omer I., Alqahtani, Abdulaziz, and Attia, Rasha A.
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Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide; therefore, searching for an effective treatment for this illness is of great importance. In the present work, in vitro cytotoxic activity of the ethanol extract of the aerial parts of Cynara cardunculus L. against human liver carcinoma cells (Hep G2) was tested. Additionally , the antitumor activity of the extract was confirmed using chemically induced rat liver carcinogenesis with diethylnitrosamine (DEN). Moreover, bioguided fractionation and column chromatographic separation of the active compounds were carried out. The extract of C. cardunculus showed a promising cytotoxic activity according to the protocols of the National Cancer Institute. Bioguided chromatographic separation of the ethanol extract of C. cardunculus led to the isolation of seven secondary metabolites including two sesquiterpene lactones as the principal active components of the methylene chloride soluble fraction, grosheimin (IC 50 = 7.49 µg/mL) and cynaropicrin (IC 50 = 13.9 µg/mL). The compounds were characterized by different spectroscopic techniques such as EI-MS, IR and NMR. Additionally, in silico analysis of the two active compounds revealed their ability to bind with caspase-3 via hydrogen bonds interactions to initiate apoptosis of cancer cells. The results shed the light on the significance of C. cardunculus as a potential source of antitumor agents. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Design, synthesis, biological evaluation, and molecular docking of novel quinazolinone EGFR inhibitors as targeted anticancer agents.
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Nofal, Zinab M., Amin, Kamelia M., Mohamed, Hanaa S., El-Kerdawy, Ahmed M., Aly, Magdy S., Habib, Basma S., and Sarhan, Alaadin E.
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MOLECULAR docking ,QUINAZOLINONES ,EPIDERMAL growth factor receptors ,ANTINEOPLASTIC agents ,CELL division ,ERLOTINIB - Abstract
A novel series of 2-methyl-3-phenylquinazolin-4-one derivatives were synthesized and biologically evaluated for their cytotoxic potential against MCF-7, HepG2, and PC-3 cancer cells. Most of the tested compounds showed reasonable safety in the normal human skin melanocyte HFB4 cell line. Compound 4 showed potent cytotoxicity on Hep-G2 cell lines, while compound 9 showed potent cytotoxicity on the MCF-7 cell line, whereas compounds 10 and 12 showed potent cytotoxicity on Hep-G2 cell lines using 5-fluorouracil as a reference standard. Cell division analysis on the tested cell lines revealed that compounds 4, 9, 10, and 12 have potent antiproliferative properties. An in vitro enzymatic inhibition assay against EGFR-TK confirmed that those compounds have potent EGFR inhibitory activity. The target compounds arrested the cell cycle at the pre-G1 and G2/M phases. Molecular docking simulations showed that all the target compounds possess a common binding pattern like that of Erlotinib. [ABSTRACT FROM AUTHOR]
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- 2022
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13. A Simple and Efficient Approach to the Synthesis of 4-Aryl-2-dialkylphosphonomethyl-4-oxobutanenitrile.
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Yaccoubi, Ferid, Elleuch, Hitham, Mohamed, Hussein S., Hamza, Zeinab S., and Zaki, Yasser H.
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MOLECULAR docking ,SARS virus ,PROGESTERONE receptors ,BINDING energy ,AROMATIC aldehydes ,NUCLEAR magnetic resonance spectroscopy ,ANTINEOPLASTIC agents - Abstract
In this work, we describe a simple and easy synthetic approach to variously 4-aryl-2-alkylphosphonomethyl-4-oxobutanenitrile based on the reaction of aromatic aldehydes with phosphorylated Michael's acceptors in good yields. A general mechanism for the reactions was also proposed. Characterization of the products was carried out by several spectroscopic tools, including Infrared and Nuclear Magnetic Resonance Spectroscopies (
1 H,13 C, and31 P-NMR). Molecular docking studies were conducted on the synthesized materials against (1UK4) the crystal structure of the SARS Coronavirus Main Proteinase (3CLpro) to study the antiviral activity of these compounds and against (1E3K) the Human Progesterone Receptor to study the anticancer activity of these compounds. We found that compound (5i) was the best one in both antiviral and anticancer activity (according to the binding energy values). [ABSTRACT FROM AUTHOR]- Published
- 2022
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14. Synthesis, Biological Evaluation, Molecular Docking, ADME Predictions and QSAR Studies of Novel 1,2-Diazet and Pyrrole Derivatives as Anti-Inflammatory Agents.
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El-Serwy, Walaa S., El-Serwy, Weam S., Mohamed, Neama A., Kassem, Emad M. M., Mostafa, Rasha E., and Mohamed, Hanaa S.
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MOLECULAR docking ,PYRROLE derivatives ,ANTI-inflammatory agents ,STRUCTURE-activity relationships ,FORECASTING ,INDOMETHACIN - Abstract
Here we synthesized novel 1, 2-diazet and pyrrole derivatives and screened for their anti-inflammatory activity. In vivo anti-inflammatory evaluation results revealed that compounds (XVI), (XIV) and (XI) exhibited the highest anti-inflammatory potencies all over the 4 hours, while compounds (VII), (V) and (XV) exhibited the lowest potencies when compared to indomethacin group. Molecular docking study was used to predict the binding mode towards c-Jun N-Terminal Kinase. In addition, ADME (absorption, distribution, metabolism, and excretion) prediction and QSAR (quantitative structure–activity relationship) study of compounds was carried out respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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15. Thiopyrimidine‐5‐carbonitrile Derivatives as VEGFR‐2 Inhibitors: Synthesis, Anticancer Evaluation, Molecular Docking, ADME Predictions and QSAR Studies.
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El‐serwy, Walaa S., Mohamed, Hanaa S., El‐serwy, Weam S., Mohamed, Neama A., Kassem, Emad M. M., Mahmoud, Khaled, and Nossier, Eman S.
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MOLECULAR docking , *CELL lines , *FORECASTING - Abstract
In this study, several novel thiopyrimidine‐5‐carbonitrile derivatives were synthesized and antitumor activity was investigated. Among them, N‐(4‐bromophenyl)‐2‐cyanoacetyl hydrazine‐1‐carbothioamide 6 revealed that the most potent cytotoxic activity against all tested cell lines, that it is why; it was subjected to in vitro kinase inhibitory assay. Molecular docking simulation was done to verify the binding mode towards VEGFR‐2 and afforded clear evidence on the observed anticancer behavior. Prediction of ADME properties and QSAR study of compounds was carried out, respectively. [ABSTRACT FROM AUTHOR]
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- 2020
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16. The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation.
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Abdelrheem, Doaa A., Ahmed, Shimaa A., Abd El-Mageed, H. R., Mohamed, Hussein S., Rahman, Aziz A., Elsayed, Khaled N. M., and Ahmed, Sayed A.
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MOLECULAR docking ,SARS-CoV-2 ,BIOACTIVE compounds ,DYNAMIC simulation ,COVID-19 ,AZITHROMYCIN - Abstract
This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1–10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski's rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment. [ABSTRACT FROM AUTHOR]
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- 2020
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17. Water-soluble Cu(II)-complexes of Schiff base amino acid derivatives as biological reagents and sufficient catalysts for oxidation reactions.
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Mohamad, Ahmad D.M., El-Shrkawy, Eman R., Al-Hussein, Maryam F.I., and Adam, Mohamed Shaker S.
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AMINO acid derivatives ,SCHIFF bases ,BIOLOGICAL reagents ,SULFONATES ,LEUCINE ,BENZYL alcohol ,MASS spectrometry ,PHENYLALANINE - Abstract
• Two novel Cu-complexes (Cu-PSA and Cu-PSL) are synthesized from two Schiff base amino acids derivatives (HPSA and HPSL). • Catalytic efficiency of Cu-PSA and Cu-PSL is studied in the (ep)oxidation of 1,2-cyclooctene and benzyl alcohol. • The biological potentials of the two ligands and their Cu
II -complexes are studied microbially. • The ct DNA interaction is investigated spectroscopically, and by viscosity-measurements and gel electrophoresis techniques. • The molecular docking studies support the nature of such interactions. Two novel water-soluble Cu(II) complexes (Cu-PSA and Cu-PSL) are synthesized from easily accessible Schiff base amino acid ligands (HPSA and HPS), as sodium sulfonate salts, obtained from D,L-phenylalanine and D,L-leucine, respectively. Their chemical composition is confirmed using various spectroscopic analyses (NMR, UV–vis, IR and mass spectroscopies, CHN micro-analyses, conductivities, TGA, and magnetism). The effect of sodium sulfonate group (Na+ SO 3− group) on the chemical behavior of both Cu-PSA and Cu-PSL complexes is studied catalytically and biologically. Catalytically, Cu-PSA and Cu-PSL exhibit high reactivity in the (ep)oxidation of 1,2-cyclooctene and benzyl alcohol in polar reaction media, (acetonitrile or water) at 80°C, under homogeneous reaction condition. Biologically, the Cu-complexes and their ligands (HPSA and HPS) are tested for antimicrobial activity against some pathogens strains. Both Cu-complexes reveal higher performance than their corresponding ligands. Cu-PSA and Cu-PSL complexes are also examined for ct DNA-interaction, which studied using various techniques including spectroscopy, viscosity and gel-electrophoresis. Despite, their low lipophilicity due to the sodium sulfonate group (salting group), they show potentially high electrostatic interaction with ct DNA. The binding potential of these compounds is also investigated by molecular docking showing the role of the central metal ion (Cu2+ ) and the salting group in the ct DNA interaction. For anticancer reactivity, both ligands (HPSA, HPSL), and their complexes (Cu-PSA or Cu-PSL) are examined against hepatocellular carcinoma (HepG2) cell line, breast carcinoma (MCF7) cell line and colon carcinoma (HCT-116) cell line. The obtained results are encouraging and after optimization the Cu-complexes could be potentially anticancer drug candidates. [ABSTRACT FROM AUTHOR]- Published
- 2020
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18. Synthesis of some novel N5‐sulfonylated and N1‐alkyated pyrazole derivatives and their antimicrobial activity in conjunction with molecular docking study.
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Metwally, Nadia H., Ragab, Eman A., and Mohamed, Mona S.
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MOLECULAR docking ,PYRAZOLE derivatives ,KLEBSIELLA pneumoniae ,ACETIC acid ,CANDIDA albicans - Abstract
Some novel N5‐sulfonylated 4 were synthesized via sulfonylation of 5‐amino‐1H‐pyrazole derivative 1 with arylsulfonyl chlorides. On the other hand, N1‐alkylated pyrazoles 7 and 10 were synthesized through alkylation of compound 1 with each of chloroacetamides and ethylchloroacetate under different conditions. Condensation of compounds 4 and 7 with different aromatic aldehydes furnished the corresponding arylidene derivatives. In spite of, condensation of 10 with aromatic aldehydes afforded the 2‐(5‐amino‐2‐aryl‐1H‐pyrazol‐1‐yl)acetic acid. The structure of the newly synthesized compounds was elucidated by elemental analyses and spectral data. Also, the suggested mechanisms for their formation were studied. Additionally, some selected new compounds were screened against antimicrobial activity. Compound 7c exhibited a higher activity against Candida albicans (inhibition zone diameter [IZD] = 31.3 ± 0.6 mm) than the standard antibiotic Nystatin (IZD = 21 ± 0.5 mm). Also, compound 7c showed minimum inhibitory concentration = 125 and 250 μg/mL against Klebsiella pneumonia and Staphylococcus aureus, respectively. Molecular docking study also was carried out for compound 7c. [ABSTRACT FROM AUTHOR]
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- 2020
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19. Molecular Docking Study of Newly Synthesized Thiopyrimidines as Antimicrobial Agents Targeting DNA Gyrase Enzyme.
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El‐serwy, Walaa S., Mohamed, Hanaa S., El‐serwy, Weam S., Mohamed, Neama A., Kassem, Emad M. M., Nossier, Eman S., and Shalaby, Al Shimaa G.
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DNA topoisomerase II , *DEOXYRIBOZYMES , *MOLECULAR docking , *ANTI-infective agents , *BINDING site assay - Abstract
A new series of thiopyrimidine‐5‐carbonitrile derivatives were synthesized and the chemical identity of them was established on the basis of spectral methods. The antimicrobial properties of all derivatives were investigated against Gram‐positive and Gram‐negative bacteria as well as fungal strains. The results of the antimicrobial screening showed that compounds 4, 11, and 12 have a higher and broad spectrum efficacy against all the tested organisms in comparison with the reference drugs. Interestingly, the most active compounds 4 and 12 showed good binding assay results with Escherichia coli DNA gyrase comparable to that of the reference, methotrexate. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, DNA gyrase. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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20. Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches.
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Abdelhameed, Ali Saber, Bakheit, Ahmed H., Mohamed, Mostafa S., Eldehna, Wagdy M., Abdel-Aziz, Hatem A., and Attia, Mohamed I.
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SERUM albumin ,MOLECULAR docking ,FLUORESCENCE spectroscopy - Abstract
As part of the research endeavors to combat cancer, a non-symmetric bis-isatin derivative (compound 3) was synthesized and showed a significant anti-proliferative potency. The current study provides a comprehensive characterization of the interaction of compound 3 with the drug-transporting protein bovine serum albumin (BSA) via the use of spectroscopic tools along with molecular docking studies. Fluorescence spectral measurements showed that the BSA intrinsic fluorescence can be significantly quenched by the addition of compound 3 and the formation of a non-fluorescent complex. Further measurements revealed a static type of quenching with Stern-Volmer and Linweaver-Burk constants of 10
5 . The thermodynamic parameters of the binding were calculated to be ΔS° 105.09 ± 5.32 with ΔH° of -0.72 ± 0.71 and negative ΔG° values. In addition, synchronous fluorescence and 3D fluorescence spectroscopy suggested that compound 3 did not induce conformational changes in BSA. Site competition experiments revealed that compound 3 competes with warfarin within the BSA binding domain (Sudlow site I). This was further confirmed by the molecular docking results showing a binding energy of -25.93 kJ/mol for compound 3-BSA. Hence, the observed results in the present study assumed that the compound 3-BSA binding is spontaneous, involving electrostatic forces and hydrogen bonding. [ABSTRACT FROM AUTHOR]- Published
- 2017
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21. Design, synthesis and molecular docking of new pyrazole-thiazolidinones as potent anti-inflammatory and analgesic agents with TNF-α inhibitory activity.
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Abd El-Karim, Somaia S., Mohamed, Hanaa S., Abdelhameed, Mohamed F., El-Galil E. Amr, Abd, Almehizia, Abdulrahman A., and Nossier, Eman S.
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MOLECULAR docking , *ANTI-inflammatory agents , *ELEMENTAL analysis , *DRUG standards , *CYTOKINES - Abstract
[Display omitted] • Synthesis of new pyrazole-methylenehydrazono-thiazolidinone derivatives 4 – 23. • In-vivo anti-inflammatory and ulcerogenic evaluation of all new compounds. • The promising derivatives were further examined as analgesics and TNF-α inhibitors. • Molecular docking of the promising compounds 5, 10, 15 and 22 was done with TNF-α. A new set of derivatives bearing pyrazole-methylenehydrazono-thiazolidinone scaffold 4 – 23 was designed, synthesized and confirmed by different spectroscopic means and elemental analyses. In-vivo anti-inflammatory and ulcerogenic evaluation was performed for all the newly synthesized derivatives using indomethacin, celecoxib and diclofenac as standard drugs. The compounds 5 , 10 , 15 , 17 , 21 , 22 appeared to be the most promising candidates producing rapid onset and long duration of anti-inflammatory activity as well as promising GIT safety profile. Furthermore, analgesic evaluation revealed that the compounds 5 , 10 , 15 and 22 produced potent and long acting analgesia accompanied with significant inhibition of the inflammatory cytokine TNF-α level in comparison with the standard drugs. Molecular docking study of the latter derivatives was also carried out to rationalize their binding affinities and their modes of interactions with the active site of TNF-α. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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22. Tailoring, structural inspection of novel oxy and non-oxy metal-imine chelates for DNA interaction, pharmaceutical and molecular docking studies.
- Author
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Adam, Mohamed Shaker S., Abu-Dief, Ahmed M., Makhlouf, M.M., Shaaban, Saad, Alzahrani, Seraj O., Alkhatib, Fatmah, Masaret, Ghada S., Mohamed, Mamdouh A., Alsehli, Mosa, El-Metwaly, Nashwa M., and Mohamad, Ahmad Desoky M.
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MOLECULAR docking , *DNA , *MEASUREMENT of viscosity , *CHELATES , *BIOLOGICAL reagents , *SULFONATES - Abstract
Two mononuclear M(II) complexes (M = Ni2+ and ZrO2+ cations) of the imino-naphthalenol sodium sulfonate ligand (H 2 Lig) were prepared and characterized via different physicochemical tools and DFT calculations. The interactions of the prepared complexes with DNA were explored. Furthermore, pharmaceutical studies on the prepared compounds were performed. [Display omitted] A green synthetic pathway for two mononuclear M(II)-complexes (M = Ni2+ as a non-oxy-metal ion and ZrO2+ as an oxy-metal ion, NiLig and ZrOLig, respectively) of an imino-naphthalenol sodium sulfonate ligand (H 2 Lig) was followed. Using various physico-chemical tools, their chemical compositions were elucidated. The material-studio package was applied to confirm the structures of NiLig and ZrOLig via the DFT method. The biological potential of the ligand (H 2 Lig) and its NiLig and ZrOLig complexes was investigated for different microbial strains as well as different cancer cell lines. The redox potential of the newly synthesized complexes was evaluated using different biochemical assays, e.g. DPPH and SOD assays. The NiLig and ZrOLig complexes exhibited improved antimicrobial and anticancer activities as compared to the free ligand (H 2 Lig). Accordingly, the ZrOLig complex was the most active biological reagent. The binding nature of the M2+ complexes to calf thymus DNA (ct DNA) was examined by UV–Vis. spectrophotometry and viscosity measurements. Both the Ni2+ and ZrO2+ complexes interestingly demonstrated anti-proliferative action against the human cancer cell lines. Such ct DNA interactions were examined theoretically by molecular docking. The approaches between the exported in-silico drug-likeness and the considered DNA interaction study were explored. The binding action between the M2+ complex and DNA would be within the electrostatic minor groove, intercalation and replacement binding modes. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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23. Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs.
- Author
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Mahmoud, Sawsan, Samaha, Doaa, Mohamed, Mosaad S., Abou Taleb, Nageh A., Elsawy, Mohamed A., Nagamatsu, Tomohisa, Ali, Hamed I., and De Rosa, Maria Cristina
- Subjects
MOLECULAR docking ,PROTEIN kinases ,BINDING energy ,DRUG design ,CELL lines - Abstract
Protein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC
50 : 0.17–2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including −43% against (FAK), −40% against (CDKI) and −36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50 . [ABSTRACT FROM AUTHOR]- Published
- 2020
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24. Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents.
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Fatahala, Samar S., Khedr, Mohammed A., and Mohamed, Mossad S.
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HETEROCYCLIC compounds , *CHEMICAL synthesis , *ANTINEOPLASTIC agents , *INDOMETHACIN , *ANTIARTHRITIC agents - Abstract
A series of fused pyrroles were synthesized and tested for their in vivo anti-inflammatory activity. Among 14 examined derivatives, 5 derivatives (1b-e, g and 5b), showed a promising anti-inflammatory activity equivalent to reference anti- inflammatory drugs (indomethacin and ibuprofen). A molecular docking study was conducted to interpret the biological activities of the tested compounds. The docking results were complementary with the phase of the biological survey and confirmed the biological effects. [ABSTRACT FROM AUTHOR]
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- 2017
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25. Synthesis, anti-inflammatory properties, molecular modelling and potential COX-2, TNF-α, PGE2 and IL1β inhibitors of pyrazole-based scaffolds.
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Srour, Aladdin M., Fahmy, Hoda H., Khater, Mai A., Zarie, Eman S., Mohamed, Sherif S., and Abdelhameed, Mohamed F.
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CYCLOOXYGENASE 2 , *GASTRIC mucosa , *MOLECULAR docking , *PYRAZOLE derivatives , *ANTI-inflammatory agents , *CARRAGEENANS - Abstract
• A variety of tri-substituted pyrazole derivatives 3 - 15 were synthesized and evaluated for their anti-inflammatory, analgesic, antipyretic and ulcerogenic properties. • Some of the tested conjugates showed promising biological observations comparable to standard reference celecoxib, in addition, to their safety margin for gastric mucosa when evaluated for their ulcer-producing activity. • The most potent derivatives 3a, 3b, 6, 8 and 11 were assayed for their COX-2, TNF-α, PGE2 and IL1β levels in rat paws using the carrageenan inflammation model with the ELISA kit. • Compound 8 possesses the best promising anti-inflammatory observations, antipyretic effect and long-lasting analgesic activity without ulcerogenic potential in addition to showing mutual inhibitory effects on all tested enzymes. • A molecular docking study was introduced to recognize the binding interactions of the most potent candidates into active sites of COX-2 and TNF-α. • Compound 8 has the best binding interaction scores with both targeted enzymes that supported its obtained bio-observations and proves that it has the potential to be developed into an anti-inflammatory drug. Starting from the precursors 3-(4-methoxyphenyl)-1H-pyrazole-4-carbaldehyde (1) and 3-(4-bromophenyl)-1-ethyl-1 H -pyrazole-4-carbaldehyde (2), a variety of trisubstituted pyrazole derivatives 3 - 15 were synthesized and evaluated for their anti-inflammatory, analgesic, antipyretic and ulcerogenic properties. Derivatives 3a, 3b, 6, 8 and 11 showed promising anti-inflammatory observations with potencies of 99.5, 100.3, 92.4, 77.1 and 103.1, respectively, compared with celecoxib the used standard reference, they also exhibited a promising onset action of analgesic with efficiency superior to the used reference drug, in addition to their antipyretic effect and safety margin for gastric mucosa compared with the reference drugs. Based on the obtained observations, derivatives 3a, 3b, 6, 8 and 11 were assayed for their COX-2, TNF- α , PGE2 and IL1 β levels in rat paws using the carrageenan inflammation model with the ELISA kit. Compound 8 has the best promising anti-inflammatory observations, antipyretic effect and long-lasting analgesic activity without ulcerogenic potential in addition to showing mutual inhibitory effects on all tested enzymes. Furthermore, a molecular docking study was introduced to recognize the binding interactions of the most potent candidates 3a, 3b, 6, 8 and 11 into the active sites of COX-2 and TNF- α. Compound 8 has the best binding interaction scores with both targeted enzymes that supported its obtained bio-observations and prove that it has the potential to be developed into an anti-inflammatory drug. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
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26. Design and synthesis of novel benzoazoninone derivatives as potential CBSIs and apoptotic inducers: In Vitro, in Vivo, molecular docking, molecular dynamics, and SAR studies.
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Hammouda, Mohamed M., Elmaaty, Ayman Abo, Nafie, Mohamed S., Abdel-Motaal, Marwa, Mohamed, Noha S., Tantawy, Mohamed A., Belal, Amany, Alnajjar, Radwan, Eldehna, Wagdy M., and Al‐Karmalawy, Ahmed A.
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MOLECULAR docking , *TUBULINS , *MOLECULAR dynamics , *BINDING sites , *STRUCTURE-activity relationships , *P53 antioncogene - Abstract
[Display omitted] • A new series of benzo[ b ]azonin-2-one derivatives (4 , 5 , 6 , 7a-d) having the same pharmacophoric features of CBSIs were designed and synthesized. • The anti-proliferative activities were examined against five selected cancer cell lines. • Both 7a and 7d compounds efficiently inhibited the β-tubulin at the CBS compared to colchicine. • Cell cycle analysis and Annexin V-based flow cytometry in the MDA-231 cell line were performed. • The apoptotic activity of 7d was investigated using gene expression analysis. • Compound 7d was directed for in vivo studies using SEC -bearing mice. • Molecular docking, molecular dynamics simulations (for 150 ns), ADMET, and toxicity in silico studies were carried out. • A very promising SAR was concluded to investigate the possible changes in the antimitotic activities upon future structural modifications. Apparently, tubulin inhibitors binding to the colchicine-binding site (CBS) currently have outstanding attention for cancer treatment. So, a series of benzo[ b ]azonin-2-one derivatives having the same pharmacophoric features as colchicine binding site inhibitors (CBSIs) were synthesized targeting the CBS of β-tubulin. The antiproliferative activities of the newly synthesized compounds were assessed against five different cancer cell lines; HepG-2, MCF-7, MDA-MB-231, HCT-116, and Caco-2. Compounds 7a and 7d displayed promising inhibitory activities against all tested cell lines. They were further estimated towards β-tubulin at CBS along with colchicine (Col) as a reference drug. It was shown that the assessed candidates (7a and 7d) and Col exhibited CBSI activities of 5492, 3771, and 486c.p.m./mg protein, respectively, at a concentration of 10 µM. Furthermore, compound 7d was picked out to assess its effects on apoptosis and cell-cycle profile using Annexin V-FITC and PI staining assay. In addition, the apoptotic activity of 7d was investigated using gene expression analysis of apoptosis-related genes of P53, Bax, Caspases 3 and 9, and Bcl-2 in both treated and untreated cells. Moreover, compound 7d was further assessed through in vivo studies using solid Ehrlich carcinoma (SEC)-bearing mice. Furthermore, both molecular docking and molecular dynamics simulations (for 150 ns) were performed to investigate their mechanism of action as potential CBSIs and give more insights into the behavior of the examined candidates within the β-tubulin subunit of the CBS. On the other hand, in silico ADMET studies were carried out to assess the pharmacokinetic features, drug/lead likeness, and toxicity parameters of the newly synthesized derivatives. Finally, to anticipate the possible changes in the antimitotic activities upon future structural modifications of the investigated compounds, a structure–activity relationship study (SAR) was accomplished. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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27. Synthesis, spectral characterization, DFT calculations, pharmacological studies, CT-DNA binding and molecular docking of potential N, O-multidentate chelating ligand and its VO(II), Zn(II) and ZrO(II) chelates.
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Abdel-Rahman, Laila H., Al–Farhan, Badriah Saad, Al Zamil, Noura O., Noamaan, Mahmoud A., El-Sayed Ahmed, Hanan, and Adam, Mohamed Shaker S.
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COORDINATION polymers , *CHELATES , *MOLECULAR docking , *SCHIFF bases , *AMINO acid residues , *PYRAMIDS (Geometry) , *ELEMENTAL analysis - Abstract
[Display omitted] • New (H 2 L) ligand derived from phenylenediamine has been synthesized and characterized. • Zr(IV), V(IV), Zn(II)-chelates have been synthesized and characterized using analytical and spectroscopic tools. • Excellent antimicrobial activity was observed against various Gram-positive and Gram-negative bacteria. • Metal chelates showed higher potent cytotoxic effect compared to the H 2 L ligand. • CT-DNA binding ability followed the order: VOL > ZrOL > ZnL(H 2 O) 2. • The new complexes have better radical scavenging potencies against DPPH radicals than H2L ligand. The pharmacological efficacy of the variety tetradentate ligands encouraged us to design attractive compounds through effective synthetic procedure. The prepared Schiff base ligand 6,6′-((1 E ,1′ E)-((4-chloro-1,2-phenylene)bis(azaneylylidene))bis(methaneylylidene))bis(2-ethoxy phenol (H 2 L), which derived from 4-chloro-o-phenylenediamine and 3-ethoxy-salicylaldehyde and its VO(II), Zn(II) and ZrO(II) metal chelates, have been synthesized and characterized with aim of that it may struggle the invasion of drug resistance. The chemical structural of studied compounds were discussed by TGA, elemental analysis, UV–Vis., 1H NMR, 13C NMR, FTIR, mass spectral, PXRD, molar conductance, magnetic susceptibility measurements and density functional theory. The results assigned square pyramid geometries for [VOL] and [ZrOL].2H 2 O chelates and an octahedral geometry for [ZnL(H 2 O) 2 ].2H 2 O chelate. Powder XRD data showed that the complexes are monoclinic with polycrystalline nature. The results of CT-DNA interaction with the titled chelates showed that the binding between CT-DNA and the metal complexes occurs through intercalation mode. Their CT-DNA binding efficiency estimated in terms of their binding constants (K b), which gave the order: VOL (6.9 × 105) > ZrOL (6.3 × 105) > ZnL(H 2 O) 2 (5.5 × 105). The antimicrobial activities of the synthesized compounds were tested against selected fungal and bacterial strains using well diffusion technique. The obtained chelates showed higher antifungal and antibacterial activities than their corresponding ligand. Furthermore, the M−complexes showed higher potent cytotoxic effect toward HEK-293, human colorectal HepG-2, HCT-116 and MCF-7 adenocarcinoma cell lines compared to the free H 2 L ligand. Investigation of antioxidant property represented that all the prepared complexes have better radical scavenging potencies against DPPH radicals than the free H 2 L ligand. To study the molecular docking of proposed compounds versus Tyrosine kinases receptor (TKR), we used AutoDock1.5.6rc3® suite. The current compounds (H 2 L, VOL, ZrOL and ZnL(H 2 O) 2) and STI were found to bind with C-kit of TKR with HBs at ILE789.A, ILE808.A, ASP810.A, GLU640.A and TYR846 amino acid residue and the binding energies were − 8.9, −8.93, −8.83, −1.48 and −10.39 kcal/mol respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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28. Isolation, characterization, in vitro anticancer activity, dft calculations, molecular docking, bioactivity score, drug-likeness and admet studies of eight phytoconstituents from brown alga sargassum platycarpum.
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Abdelrheem, Doaa A., Rahman, Aziz A., Elsayed, Khaled N.M., Abd El-Mageed, H.R., Mohamed, Hussein S., and Ahmed, Sayed A.
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MOLECULAR docking , *PALMITIC acid , *BROWN algae , *OLEIC acid , *SARGASSUM , *ANTINEOPLASTIC agents , *MARINE algae - Abstract
• Isolation and characterization of eight bioactive compounds from brown alga sargassum platycarpum for the first time. • Evaluation of the in vitro anticancer activity against HepG-2 cell line. • Computations of MEP, EHOMO, ELUMO and global properties by DFT methods. • Molecular docking study. • Bioactivity Score, drug-likeness and ADMET studies. Image, graphical abstract Recently, macroalgae or seaweeds serve as a treasure of potential drugs for cancer therapy. The present study investigated the cytotoxic activity of eight compounds isolated from the brown alga Sargassum platycarpum for the first time. These isolates were identified as hexadecanoic acid (1), oleic acid (2), saringosterol (3 and 4 , 1:1 mixture of C-24epimers), β -sitosterol (5), glycoglycerolipid (6), loliolide (7) and Kjellmanianone (8) by spectroscopic techniques. Two epimers of saringosterol, (24- R)-saringosterol (3) and (24- S)-saringosterol (4), were subsequently separated by HPLC. (24- S)-saringosterol (4) and (24- R)-saringosterol (3) exhibited potent cytotoxicity against HepG-2 cells with IC 50 of 0.10±0.00 and 0.11±0.00 µM, respectively with compared to standard 5-Fluorouracil (IC 50 of 0.63±0.28 µM) and other isolates. MEP, E HOMO , E LUMO and global properties of all isolated compounds are computed by DFT methods. Molecular docking study showed that most of the isolated compounds especially compounds 3 and 4 interact strongly with 4PYP with the highest binding energies maintained that the high cytotoxic activity of these compounds against HepG-2 cells in the experimental part. Bioactivity Score, Drug-Likeness and ADMET studies supported the potential biological activities of most isolated compounds especially compounds 3 and 4 and also created attention for developing them to act as good candidates. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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