Publications by authors named "Mohamed F Zayed"

18 Publications

  • Page 1 of 1

In vivo- and in silico-driven identification of novel synthetic quinoxalines as anticonvulsants and AMPA inhibitors.

Arch Pharm (Weinheim) 2021 May 9;354(5):e2000449. Epub 2021 Feb 9.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Menoufia University, Shebin El-Koum, Egypt.

The lack of effective therapies for epileptic patients and the potentially harmful consequences of untreated seizure incidents have made epileptic disorders in humans a major health concern. Therefore, new and more potent anticonvulsant drugs are continually sought after, to combat epilepsy. On the basis of the pharmacophoric structural specifications of effective α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists with an efficient anticonvulsant activity, the present work reports the design and synthesis of two novel sets of quinoxaline derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo according to the pentylenetetrazol-induced seizure protocol, and the results were compared with those of perampanel as a reference drug. Among the synthesized compounds, 24, 28, 32, and 33 showed promising activities with ED values of 37.50, 23.02, 29.16, and 23.86 mg/kg, respectively. Docking studies of these compounds suggested that AMPA binding could be the mechanism of action of these derivatives. Overall, the pharmacophore-based structural optimization, in vivo and in silico docking, and druglikeness studies indicated that the designed compounds could serve as promising candidates for the development of effective anticonvulsant agents with good pharmacokinetic profiles.
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http://dx.doi.org/10.1002/ardp.202000449DOI Listing
May 2021

Design, synthesis, in silico ADMET profile and GABA-A docking of novel phthalazines as potent anticonvulsants.

Arch Pharm (Weinheim) 2019 May 15;352(5):e1800387. Epub 2019 Apr 15.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

A new series of 2-substituted-2,3-dihydrophthalazine-1,4-diones (2- 9) were designed and synthesized to evaluate their anticonvulsant activity. The neurotoxicity was assessed using the rotarod test. Molecular docking was performed for the synthesized compounds to assess their binding affinities as γ-aminobutyric acid A (GABA-A) receptor agonists as a possible mechanism of their anticonvulsant action, to rationalize their anticonvulsant activity in a qualitative way. The data obtained from the molecular modeling was strongly matched with that obtained from the biological screening, which revealed that compounds 5 , 9 , and 9 showed the highest binding affinities toward the GABA-A receptor and also showed the highest anticonvulsant activities with relative potencies of 1.66, 1.63, and 1.61, respectively, compared with diazepam. The most active compounds 5 , 9 , and 9 were further tested against maximal electroshock seizures. Compounds 5 and 9 showed 100% protection at a dose level of 125 µg/kg, while compound 9 exhibited 83.33% protection at the same dose level. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and to explain the possible mechanism for their anticonvulsant action. These agents exerted low neurotoxicity and a high safety margin compared with valproate as a reference drug. Most of our designed compounds exhibited a good ADMET profile.
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http://dx.doi.org/10.1002/ardp.201800387DOI Listing
May 2019

Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones.

Med Chem 2019 ;15(6):659-675

Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.

Background: Quinazolines and quinazolinones derivatives are well known for their important range of therapeutic activities.

Objective: The study aims to carry out the synthesis of some derivatives of substituted fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal, and anti-biofilm activities.

Methods: Compounds were chemically synthesized by conventional methods. Structures were established on the basis of spectral and elemental analyses. The antimicrobial potential was tested against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational studies were performed using Auto dock free software package (version 4.0) to explain the predicted mode of binding.

Results: All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives with their receptor-site and detected their predicted mode of binding.

Conclusion: The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm activities. Modeling study explained their binding mode and showed strong binding affinity with their receptor-site. The highly active compounds 5 and 10c could be subjected to future optimization and investigation to be effective antimicrobial agents.
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http://dx.doi.org/10.2174/1573406414666181109092944DOI Listing
October 2019

Tagetnoic acid, a new lipoxygenase inhibitor peroxy fatty acid from growing in Saudi Arabia.

Nat Prod Res 2020 Feb 8;34(4):474-481. Epub 2018 Oct 8.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

A new peroxy fatty acid, tagetnoic acid () [4-((3,6)-6-((3,8)-octadeca-3,8-dien-1-yl)-3,6-dihydro-1,2-dioxin-3-yl)butanoic acid] and four known metabolites: ecliptal (5-formyl--terthiophene) (), 5-(4-hydroxybut-1-ynyl)-2,2'-bithiophene (), 22,23-dihydrospinasterone (), and stigmasterol () were separated from the -hexane fraction of the aerial parts of L. (Asteraceae). Their chemical structures were verified using IR, UV, 2D and 1D NMR, and HRMS. Compounds displayed potent lipoxygenase inhibitory potential with ICs 2.26, 1.83, and 1.17 μM, respectively compared to indomethacin (IC 0.89 μM). Moreover, molecular docking study revealed that the potent activity of is due to H-bonding and hydrophobic interaction. The results of this study suggested that dietary consumption would be useful for the individuals at risk of acute and chronic inflammatory disorders.
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http://dx.doi.org/10.1080/14786419.2018.1488712DOI Listing
February 2020

Quinazolinone-Amino Acid Hybrids as Dual Inhibitors of EGFR Kinase and Tubulin Polymerization.

Molecules 2018 Jul 12;23(7). Epub 2018 Jul 12.

Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah 41477, Al-Munawarah, Saudi Arabia.

Some fluoroquinazolinones (⁻) were designed, synthesized and biologically evaluated for their antitumor activity against the two cell lines, MCF-7 and MDA-MBA-231. New derivative (IC = 0.44 ± 0.01 µM) showed antitumor activity, better than that of the reference drug erlotinib (IC = 1.14 ± 0.04 µM) against MCF-7. New derivative (IC = 0.43 ± 0.02 µM) showed higher activity than the reference drug erlotinib (IC = 2.55 ± 0.19 µM) against MDA-MBA-231. Furthermore, the EGFR (epidermal growth factor receptor) and tubulin inhibition assays were carried out for the highest active derivatives to reveal the expected mechanism of action. They exhibited significant results compared to the reference drugs. Molecular docking simulations were performed on EGFR and tubulin binding sites to rationalize the experimental results and describe their binding modes. The results of the molecular modeling study were correlated with that of the antitumor screening.
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http://dx.doi.org/10.3390/molecules23071699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100557PMC
July 2018

Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects.

Int J Mol Sci 2018 06 11;19(6). Epub 2018 Jun 11.

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia.

A series of new fluoroquinazolinone ⁻ and ⁻ derivatives was designed, prepared and screened for their in vitro cytotoxic activity against human cancer cell lines MCF-7 and MDA-MBA-231. Compounds (IC = 0.35 ± 0.01 µM), (IC = 0.71 ± 0.01 µM), (IC = 0.89 ± 0.02 µM) and (IC = 0.95 ± 0.01 µM) displayed broad spectrum anticancer activity better than the reference drug gefitinib (IC = 0.97 ± 0.02 µM) against MCF-7. Compounds (IC = 0.28 ± 0.02 µM), (IC = 0.38 ± 0.01 µM), (IC = 0.94 ± 0.07 µM) and (IC = 1.09 ± 0.01 µM) showed better activity than the reference gefitinib (IC = 1.30 ± 0.04 µM) against MDA-MBA-231. Moreover, EGFR and tubulin inhibition assays were performed for the highest active derivatives and showed remarkable results comparing to the reference drugs. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated.
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http://dx.doi.org/10.3390/ijms19061731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032053PMC
June 2018

Biologically active fungal depsidones: Chemistry, biosynthesis, structural characterization, and bioactivities.

Fitoterapia 2018 Sep 25;129:317-365. Epub 2018 Apr 25.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Fungi produce a wide range of structurally unique metabolites. Depsidones represent one of the most interesting classes of metabolites, consisting of two 2,4-dihydroxybenzoic acid rings linked together by both ether and ester bonds. Naturally occurring depsidones are produced by lichen, fungi, and plants. They possessed a wide array of bioactivities, including antioxidant, antiproliferative, antimalarial, cytotoxic, antibacterial, radical scavenging, antihypertensive, anti-inflammatory, antifungal, and aromatase and protein kinase inhibitory. In order to point out the potential of this class of compounds, the present review focuses only on the depsidones that have been isolated from fungal source and published from 1978 to 2018. This review outlined the research on the biosynthesis, source, isolation, spectral and physical data, and bioactivities of the naturally occurring fungal depsidones. On the basis of 88 references, > 80 compounds have been described.
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http://dx.doi.org/10.1016/j.fitote.2018.04.012DOI Listing
September 2018

Potential Anti-Malarial Agents from Endophytic Fungi: A Review.

Mini Rev Med Chem 2018 ;18(13):1110-1132

Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah Al Munawwarah 30078, Saudi Arabia.

Malaria is one of the major infectious diseases and foremost cause of mortality and morbidity in many subtropical and tropical regions. In the last years, the situation has become worst in many ways, due to increase in the parasites resistance to various available antimalarial agents. Furthermore, malaria`s control is beginning to be more sophisticated by the parallel spread of mosquito vector`s resistance to the available insecticides. Recently, there is a wide consensus to seek for target specific, safe, affordable, and effective new antimalarial agents, which can compete with synthetic ones. Endophytic fungi are of a growing interest as prominent sources of structurally unique bioactive natural products. The bio-metabolites isolated from endophytic fungi, possessing antimalarial potential may compose the base for the synthesis of novel drugs that might be utilized to withstand malaria and its resistance. For getting information on the various studies, PubMed, Google Scholar, ScienceDirect, SpringerLink, Scopus, and Wiley search was done using keywords (malaria, endophytic fungi, and antimalarial activity). The present review covers the literature published from 1996 to 2017 and highlights the metabolites for which antimalarial activities have been reported. Overall, 135 fungal metabolites and 72 references are cited. In addition, their structure, chemical class, fungal source, host, and activity have been presented. This review shows the significance of endophytic fungi as a wealthy pool of antimalarial agents.
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http://dx.doi.org/10.2174/1389557518666180305163151DOI Listing
July 2018

The Design and Development of Potent Small Molecules as Anticancer Agents Targeting EGFR TK and Tubulin Polymerization.

Int J Mol Sci 2018 Jan 30;19(2). Epub 2018 Jan 30.

Pharmacognosy and Pharmaceutical Chemistry Department, Pharmacy College, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia.

Some novel anthranilate diamides derivatives -, - and - were designed and synthesized to be evaluated for their in vitro anticancer activity. Structures of all newly synthesized compounds were confirmed by infra-red (IR), high-resolution mass (HR-MS) spectra, ¹H nuclear magnetic resonance (NMR) and C nuclear magnetic resonance (NMR) analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using erlotinib as a reference drug against two different types of breast cancer cells. The molecular docking study was performed for representative compounds against two targets, epidermal growth factor receptor (EGFR) and tubulin in colchicine binding site to assess their binding affinities in order to rationalize their anticancer activity in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the anthranilate diamide showed excellent activity with nanomolar or sub nanomolar half maximal inhibitory concentration (IC) values against tumor cells. EGFR tyrosine kinase (TK) inhibition assay, tubulin inhibition assay and apoptosis analysis were performed for selected compounds to get more details about their mechanism of action. Extensive structure activity relationship (SAR) analyses were also carried out.
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http://dx.doi.org/10.3390/ijms19020408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855630PMC
January 2018

Fusarithioamide B, a new benzamide derivative from the endophytic fungus Fusarium chlamydosporium with potent cytotoxic and antimicrobial activities.

Bioorg Med Chem 2018 02 30;26(3):786-790. Epub 2017 Dec 30.

National Center for Natural Products Research, Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.

Fusarithioamide B (6), a new aminobenzamide derivative with unprecedented carbon skeleton and five known metabolites: stigmast-4-ene-3-one (1), stigmasta-4,6,8(14),22-tetraen-3-one (2), p-hydroxyacetophenone (3), tyrosol (4), and fusarithioamide A (5) were separated from Fusarium chlamydosporium EtOAc extract isolated from Anvillea garcinii (Burm.f.) DC. leaves (Asteraceae). The structure elucidation and completeassignment of the isolated metabolites were performed mainly by the aid of various NMR and MS data. Fusarithioamide B (6) has been assessed for antibacterial and antifungal activities towards various microbial strains by disc diffusion assay. It exhibited selective antifungal activity towards C. albicans (MIC 1.9 µg/ml and IZD 14.5 mm), comparing to clotrimazole (MIC 2.8 µg/ml and IZD 17.9 mm). Also, it possessed high antibacterial potential towards E. coli, B. cereus, and S. aureus compared to ciprofloxacin. Furthermore, 6 was tested for the in vitro cytotoxic effect against KB, HCT-116, BT-549, MCF-7, SKOV-3, and SK-MEL cell lines. It had selective and potent effect towards BT-549, MCF-7, SKOV-3, and HCT-116 cell lines with ICs 0.09, 0.21, 1.23, and 0.59 μM, respectively compared to doxorubicin (ICs 0.046, 0.05, 0.321, and 0.24 μM, respectively). Fusarithioamide B may provide a lead molecule for future developing of antitumor and antimicrobial agents.
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http://dx.doi.org/10.1016/j.bmc.2017.12.049DOI Listing
February 2018

Mangostanaxanthone VII, a new cytotoxic xanthone from Garcinia mangostana.

Z Naturforsch C J Biosci 2018 Apr;73(5-6):185-189

National Center for Natural Products Research, Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, Mississippi 38677, USA.

Garcinia mangostana L. (the queen of fruits, mangosteen, family Guttiferae) is a wealthy source of xanthones. The CHCl3 soluble fraction of the air-dried pericarps of G. mangostana provided a new xanthone: mangostanaxanthone VII (5), along with four known xanthones: mangostanaxanthones I (1) and II (2), gartanin (3) and γ-mangostin (4). The structural verification of these metabolites was achieved by different spectral techniques, including UV, IR, 1D and 2D NMR and HRESIMS. The new metabolite was assessed for cytotoxic potential, using sulforhodamine B (SRB) assay towards the A549 and MCF-7 cancer cell lines. Moreover, its antimicrobial effects were evaluated against various bacterial and fungal strains, using agar disc diffusion assay. Mangostanaxanthone VII showed moderate cytotoxic activity against the A549 and MCF7 cell lines with IC50s 26.1 and 34.8 μM, respectively, compared with doxorubicin (0.74 and 0.41 μM, respectively).
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http://dx.doi.org/10.1515/znc-2017-0122DOI Listing
April 2018

Rational design, synthesis, pharmacophore modeling, and docking studies for identification of novel potent DNA-PK inhibitors.

Bioorg Chem 2017 06 2;72:234-247. Epub 2017 May 2.

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; Department of Pharmaceutical and Medicinal Chemistry, Pharmacy College, Misr University for Science and Technology, Cairo, Egypt.

Drugs of cancer based upon ionizing radiation or chemotherapeutic treatment may affect breaking of DNA double strand in cell. DNA-PK enzyme has emerged as an attractive target for drug discovery efforts toward DNA repair pathways. Hence, the search for potent and selective DNA-PK inhibitors has particularly considered state-of-the art and several series of inhibitors have been designed. In this article, a novel benchmark DNA-PK database of 43 compounds was built and described. Ligand-based approaches including pharmacophore and QSAR modeling were applied and novel models were introduced and analyzed for predicting activity test for DNA-PK drug candidates. Based upon the modeling results, we gave a report of synthesis of fifteen novel 2-((8-methyl-2-morpholino-4-oxo-4H-benzo[e][1,3]oxazin-7-yl)oxy)acetamide derivatives and in vitro evaluation for DNA-PK inhibitory and antiproliferative activities. These fifteen compounds overall are satisfied with Lipinski's rule of five. The biological testing of target compounds showed five promising active compounds 7c, 7d, 7f, 9e and 9f with micromolar DNA-PK activity range from 0.25 to 5µM. In addition, SAR of the compounds activity was investigated and confirmed that the terminal aryl moiety was found to be quite crucial for DNA-PK activity. Moreover flexible docking simulation was done for the potent compounds into the putative binding site of the 3D homology model of DNA-PK enzyme and the probable interaction model between DNA-PK and the ligands was investigated and interpreted.
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http://dx.doi.org/10.1016/j.bioorg.2017.04.014DOI Listing
June 2017

Fusaripeptide A: new antifungal and anti-malarial cyclodepsipeptide from the endophytic fungus Fusarium sp.

J Asian Nat Prod Res 2018 Jan 27;20(1):75-85. Epub 2017 Apr 27.

c Department of Natural Products and Alternative Medicine, Faculty of Pharmacy , King Abdulaziz University , Jeddah 21589 , Saudi Arabia.

From the culture of the endophytic fungus Fusarium sp. isolated from the roots of Mentha longifolia L. (Labiatae) growing in Saudi Arabia, a new cyclodepsipeptide, namely fusaripeptide A (1), along with three known compounds adenosine (2), 2[(2-hydroxypropionyl)amino]benzamide (3), and cyclopentanol (4), have been isolated. Their structures were determined, using extensive 1D and 2D NMR and HRESI and GC mass spectral data. That is the first report for the isolation of compound 4 from natural source. In addition, compounds 2 and 3 are reported here for the first time from Fusarium sp. The absolute configuration of the amino acid residues of 1 was assigned by chiral GCMS and Marfey's analysis after acid hydrolysis. Fusaripeptide A differs from the reported ones from Fusarium sp. in the length of fatty acidic alkyl chain. Compound 1 was evaluated for its antifungal, anti-malarial, and cytotoxic activities. It exhibited potent antifungal activity toward C. albicans, C. glabrata, C. krusei, and A. fumigates with IC values of 0.11, 0.24, 0.19, and 0.14 μM, respectively. Furthermore, it had significant anti-malarial activity toward P. falciparum (D6 clone) with IC value of 0.34 μM. However, it showed cytotoxic activity toward the tested cell lines.
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http://dx.doi.org/10.1080/10286020.2017.1320989DOI Listing
January 2018

Synthesis, Modelling, and Anticonvulsant Studies of New Quinazolines Showing Three Highly Active Compounds with Low Toxicity and High Affinity to the GABA-A Receptor.

Molecules 2017 Jan 24;22(2). Epub 2017 Jan 24.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.

Some novel fluorinated quinazolines (-) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds , , and showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.
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http://dx.doi.org/10.3390/molecules22020188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155771PMC
January 2017

8-Hydroxyirilone 5-methyl ether and 8-hydroxyirilone, new antioxidant and α-amylase inhibitors isoflavonoids from Iris germanica rhizomes.

Bioorg Chem 2017 02 30;70:192-198. Epub 2016 Dec 30.

National Center for Natural Products Research, Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, MS 38677, USA.

Iris species are well recognized as wealthy sources of isoflavonoids. In the present study, phytochemical investigation of the rhizomes of Iris germanica (Iridaceae) procure the isolation of two new isoflavonoids namely, 8-hydroxyirilone 5-methyl ether (2) and 8-hydroxyirilone (3), along with eight known isoflavonoids: irilone 4'-methyl ether (1), irilone (4), irisolidone (5), irigenin S (6), irigenin (7), irilone 4'-O-β-d-glucopyranoside (8), iridin S (9), and iridin (10). The isolated flavonoids were structurally characterized with the assist of comprehensive spectroscopic analyses (UV, IR, 1D and 2D NMR, and HRMS) and comparing with the published data. They were estimated for their antioxidant and antidaibetic capacities using DPPH and α-amylase inhibition assays, respectively. Compounds 2, 3, and 4 exhibited prominent antioxidant activities with IC values of 12.92, 9.23, and 10.46μM, respectively compared to propyl gallate (IC 7.11μM). Moreover, 2-5 possessed highest α-amylase inhibitory activity with % inhibition 66.1, 78.3, 67.3, and 70.1, respectively in comparison to acarbose (reference α-amylase inhibitor). Additionally, their structure-activity relationship has been discussed.
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http://dx.doi.org/10.1016/j.bioorg.2016.12.010DOI Listing
February 2017

Design, Synthesis, Antimicrobial Evaluation and Molecular Modeling Study of 1,2,4-Triazole-Based 4-Thiazolidinones.

Molecules 2016 Apr 30;21(5). Epub 2016 Apr 30.

Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

A series of 3-(2H-1,2,4-triazol-5-yl)-1,3-thiazolidin-4-one derivatives (7c-l) was designed and synthesized. Their structures have been elucidated based on analytical and spectral data. They were evaluated for their antibacterial and antifungal activities. Compound 7h showed the highest activity against all tested strains, except P. vulgaris, with MIC 8 μg/mL and 4 μg/mL against S. aureus and C. albicans, respectively. Furthermore, Compounds 7c, 7h, and 7j demonstrated moderate anti-mycobacterium activity. The binding mode of the synthesized thiazolidinones to bacterial MurB enzyme was also studied. Good interactions between the docked compounds to the MurB active site were observed primarily with Asn83, Arg310, Arg188 and Ser82 amino acid residues.
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http://dx.doi.org/10.3390/molecules21050568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272934PMC
April 2016

Self Organizing Map-Based Classification of Cathepsin k and S Inhibitors with Different Selectivity Profiles Using Different Structural Molecular Fingerprints: Design and Application for Discovery of Novel Hits.

Molecules 2016 Jan 30;21(2):175. Epub 2016 Jan 30.

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, P. O. Box 30039, Al-Madinah Al-Munawarah 41477, Saudi Arabia.

The main step in a successful drug discovery pipeline is the identification of small potent compounds that selectively bind to the target of interest with high affinity. However, there is still a shortage of efficient and accurate computational methods with powerful capability to study and hence predict compound selectivity properties. In this work, we propose an affordable machine learning method to perform compound selectivity classification and prediction. For this purpose, we have collected compounds with reported activity and built a selectivity database formed of 153 cathepsin K and S inhibitors that are considered of medicinal interest. This database has three compound sets, two K/S and S/K selective ones and one non-selective KS one. We have subjected this database to the selectivity classification tool 'Emergent Self-Organizing Maps' for exploring its capability to differentiate selective cathepsin inhibitors for one target over the other. The method exhibited good clustering performance for selective ligands with high accuracy (up to 100 %). Among the possibilites, BAPs and MACCS molecular structural fingerprints were used for such a classification. The results exhibited the ability of the method for structure-selectivity relationship interpretation and selectivity markers were identified for the design of further novel inhibitors with high activity and target selectivity.
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http://dx.doi.org/10.3390/molecules21020175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272978PMC
January 2016

Synthesis and biological evaluation studies of novel quinazolinone derivatives as antibacterial and anti-inflammatory agents.

Saudi Pharm J 2014 Apr 6;22(2):157-62. Epub 2013 Apr 6.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt ; Department of Pharmacy, College of Medical Rehabilitation Sciences, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.

Some novel 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones bearing sulfonamide derivatives (4-11) were synthesized in good yields and evaluated for their possible antibacterial, anti-inflammatory activities and acute toxicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Their antibacterial activities were evaluated by the agar well diffusion method while their anti-inflammatory activities were evaluated by the carrageenan-induced hind paw edema test. All the tested compounds showed considerable antibacterial activities and high to moderate anti-inflammatory activities that last for 12 h compared to ibuprofen. All the tested compounds showed no toxic symptoms or mortality rates 24 h post-administration at tested anti-inflammatory doses. In addition, LD50 for all tested compounds was higher than that for ibuprofen implying their good safety margin. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs.
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http://dx.doi.org/10.1016/j.jsps.2013.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950501PMC
April 2014
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