Publications by authors named "Mohamed R Aouad"

12 Publications

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Design of molecular hybrids of phthalimide-triazole agents with potent selective MCF-7/HepG2 cytotoxicity: Synthesis, EGFR inhibitory effect, and metabolic stability.

Bioorg Chem 2021 Jun 22;111:104835. Epub 2021 Mar 22.

Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt.

This study reports an efficient and convenient click chemistry synthesis of a novel series of phthalimide scaffold linked to 1,2,3 triazole ring and terminal lipophilic fragments. Structures of newly synthesized compounds were well characterized by different spectroscopic tools. In vitro MTT cytotoxicity assay was performed comparing the cytotoxic effects of newly synthesized compounds to staurosporine using three different types: human liver cancer cell line (HepG2), Michigan cancer foundation-7 (MCF-7) and human colorectal carcinoma cell line (HCT116). The initial screening showed excellent to moderate anticancer activity for these newly synthesized compounds with high degree of cell line selectivity with micromolar (µM) half maximal inhibitory concentration (IC) values against tumor cells. The SAR analysis of these derivatives confirmed the role of molecular fragments including phthalimide, linker, triazole, and terminal tails in correlation to activity. In addition, enzymatic inhibitory assay against wild type EGFR was performed for the most active compounds to get more details about their mechanism of action. In order to further explore their binding affinities, molecular docking simulation was studied against EGFR site. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. One of the most prominent analogs is (6f) with terminal disubstituted ring and amide linker showed selective MCF-7 cytotoxicity profile with IC 0.22 µM and 79 nM to EGFR target. Extensive structure activity relationship (SAR) analyses were also carried out. The pharmacokinetic profile of (6f) was studied showing good metabolic stability and long duration behavior. This design offered a potent selective anticancer phthalimide-triazole leads for further optimization in cancer drug discovery.
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http://dx.doi.org/10.1016/j.bioorg.2021.104835DOI Listing
June 2021

Design, Synthesis and Anticancer Screening of Novel Benzothiazole-Piperazine-1,2,3-Triazole Hybrids.

Molecules 2018 Oct 27;23(11). Epub 2018 Oct 27.

Faculty of Science, Al al-Bayt University, Al-Mafraq 25113, Jordan.

A library of novel regioselective 1,4-di and 1,4,5-trisubstituted-1,2,3-triazole based benzothiazole-piperazine conjugates were designed and synthesized using the click synthesis approach in the presence and absence of the Cu(I) catalyst. Some of these 1,2,3-triazole hybrids possess in their structures different heterocyclic scaffold including 1,2,4-triazole, benzothiazole, isatin and/or benzimidazole. The newly designed 1,2,3-triazole hybrids were assessed for their antiproliferative inhibition potency against four selected human cancer cell lines (MCF7, T47D, HCT116 and Caco2). The majority of the synthesized compounds demonstrated moderate to potent activity against all the cancer cell lines examined. Further, we have established a structure activity relationship with respect to the in silico analysis of ADME (adsorption, distribution, metabolism and excretion) analysis and found good agreement with in vitro activity.
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http://dx.doi.org/10.3390/molecules23112788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278665PMC
October 2018

Microwave-Assisted Synthesis of Some Potential Bioactive Imidazolium-Based Room-Temperature Ionic Liquids.

Molecules 2018 Jul 15;23(7). Epub 2018 Jul 15.

Department of Chemistry, Taibah University, Al-Madina Al-Mounawara 30002, Saudi Arabia.

An environmentally-friendly and easy synthesis of a series of novel functionalized imidazolium-based ionic liquids (ILs) is described under both the conventional procedure and microwave irradiation. The structures of newly synthesized room-temperature ionic liquids (RTILs) were established by different spectral analyses. All ILs (⁻) were screened for their in vitro antimicrobial activity against a panel of clinically isolated bacteria. The results of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) showed that some of the tested ILs are very promising anti-bacterial agents especially those containing an alkyl chain with a phenyl group (most notably , , , and ).
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http://dx.doi.org/10.3390/molecules23071727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099736PMC
July 2018

Synthesis and crystal structure of a new pyridinium bromide salt: 4-methyl-1-(3-phen-oxy-prop-yl)pyridinium bromide.

Acta Crystallogr E Crystallogr Commun 2017 Dec 3;73(Pt 12):1831-1834. Epub 2017 Nov 3.

Department of Chemistry, Taibah University, 30002, Al-Madina Al-Mounawara, Saudi Arabia.

In the cation of the title mol-ecular salt, CHNO·Br, the pyridinium and phenyl rings are inclined to one another by 11.80 (8)°. In the crystal, the Br anion is linked to the cation by a C-H⋯Br hydrogen bond. The cations stack along the -axis direction and are linked by further C-H⋯Br inter-actions, and offset π-π inter-actions [inter-centroid distances = 3.5733 (19) and 3.8457 (19) Å], forming slabs parallel to the plane. The effects of the C-H⋯ inter-action on the NMR signals of the and pyridinium protons in a series of related ionic liquids, . 4-methyl-1-(4-phen-oxy-but-yl)pyridin-1-ium salts, are reported and discussed.
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http://dx.doi.org/10.1107/S2056989017015481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730234PMC
December 2017

Green Ultrasound versus Conventional Synthesis and Characterization of Specific Task Pyridinium Ionic Liquid Hydrazones Tethering Fluorinated Counter Anions: Novel Inhibitors of Fungal Ergosterol Biosynthesis.

Molecules 2017 Nov 7;22(11). Epub 2017 Nov 7.

Department of Chemistry, Faculty of Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 30002, Saudi Arabia.

A series of specific task ionic liquids (ILs) based on a pyridiniumhydrazone scaffold in combination with hexafluorophosphate (PF₆), tetrafluoroboron (BF₄) and/or trifluoroacetate (CF₃COO) counter anion, were designed and characterized by IR, NMR and mass spectrometry. The reactions were conducted under both conventional and green ultrasound procedures. The antifungal potential of the synthesized compounds - was investigated against 40 strains of (four standard and 36 clinical isolates). Minimum inhibitory concentrations (MIC) of the synthesized compounds were in the range of 62.5-2000 μg/mL for both standard and oral isolates. MIC results showed that the synthesized 1-(2-(4-chlorophenyl)-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-pyridin-1-ium hexafluorophosphate () was found to be most effective, followed by 4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-1-(2-(4-nitrophenyl)-2-oxoethyl)-pyridin-1-ium hexafluorophosphate () and 1-(2-ethoxy-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)pyridin-1-ium hexafluorophosphate (). All the isolates showed marked sensitivity towards the synthesized compounds. Ergosterol content was drastically reduced by more active synthesized compounds, and agreed well with MIC values. Confocal scanning laser microscopy (CLSM) results showed that the red colored fluorescent dye enters the test agent treated cells, which confirms cell wall and cell membrane damage. The microscopy results obtained suggested membrane-located targets for the action of these synthesized compounds. It appears that the test compounds might be interacting with ergosterol in the fungal cell membranes, decreasing the membrane ergosterol content and ultimately leading to membrane disruption as visible in confocal results. The present study indicates that these synthesized compounds show significant antifungal activity against which forms the basis to carry out further in vivo experiments before their clinical use.
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http://dx.doi.org/10.3390/molecules22111532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150352PMC
November 2017

An Eco-Friendly Ultrasound-Assisted Synthesis of Novel Fluorinated Pyridinium Salts-Based Hydrazones and Antimicrobial and Antitumor Screening.

Int J Mol Sci 2016 May 21;17(5). Epub 2016 May 21.

Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21500, Egypt.

The present work reports an efficient synthesis of fluorinated pyridinium salts-based hydrazones under both conventional and eco-friendly ultrasound procedures. The synthetic approach first involves the preparation of halogenated pyridinium salts through the condensation of isonicotinic acid hydrazide (1) with p-fluorobenzaldehyde (2) followed by the nucleophilic alkylation of the resulting N-(4-fluorobenzylidene)isonicotinohydrazide (3) with a different alkyl iodide. The iodide counteranion of 5-10 was subjected to an anion exchange metathesis reaction in the presence of an excess of the appropriate metal salts to afford a new series of fluorinated pyridinium salts tethering a hydrazone linkage 11-40. Ultrasound irradiation led to higher yields in considerably less time than the conventional methods. The newly synthesized ILs were well-characterized with FT-IR, ¹H NMR, (13)C NMR, (11)B, (19)F, (31)P and mass spectral analyses. The ILs were also screened for their antimicrobial and antitumor activities. Within the series, the salts tethering fluorinated counter anions 11-13, 21-23, 31-33 and 36-38 were found to be more potent against all bacterial and fungal strains at MIC 4-8 µg/mL. The in vitro antiproliferative activity was also investigated against four tumor cell lines (human ductal breast epithelial tumor T47D, human breast adenocarcinoma MCF-7, human epithelial carcinoma HeLa and human epithelial colorectal adenocarcinoma Caco-2) using the MTT assay, which revealed that promising antitumor activity was exhibited by compounds 5, 12 and 14.
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http://dx.doi.org/10.3390/ijms17050766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881586PMC
May 2016

Synthesis of Novel 2,5-Disubstituted-1,3,4-thiadiazoles Clubbed 1,2,4-Triazole, 1,3,4-Thiadiazole, 1,3,4-Oxadiazole and/or Schiff Base as Potential Antimicrobial and Antiproliferative Agents.

Molecules 2015 Sep 2;20(9):16048-67. Epub 2015 Sep 2.

Department of Chemistry, Faculty of Sciences, Taibah University, P. O. Box 344, Al-Madinah Al-Munawarah 30002, Saudi Arabia.

In the present study, a new series of 2,5-disubstituted-1,3,4-thiadiazole tethered 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and Schiff base derivatives were synthesized and characterized by IR, ¹H-NMR, (13)C-NMR, MS and elemental analyses. All compounds were screened for their antibacterial, antifungal and antiproliferative activity. Some of the synthesized derivatives have displayed promising biological activity.
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http://dx.doi.org/10.3390/molecules200916048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331880PMC
September 2015

Synthesis, characterization and antimicrobial evaluation of some new schiff, mannich and acetylenic Mannich bases incorporating a 1,2,4-triazole nucleus.

Authors:
Mohamed R Aouad

Molecules 2014 Nov 18;19(11):18897-910. Epub 2014 Nov 18.

Department of Chemistry, Faculty of Sciences, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia.

A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluoro-phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl2 furnished the desired acetylenic Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, 1H- and 13C-NMR) data and evaluated for their biological activities. Some of the compounds were found to exhibit significant antimicrobial activity.
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http://dx.doi.org/10.3390/molecules191118897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271917PMC
November 2014

New eco-friendly 1-alkyl-3-(4-phenoxybutyl) imidazolium-based ionic liquids derivatives: a green ultrasound-assisted synthesis, characterization, antibacterial activity and POM analyses.

Molecules 2014 Aug 7;19(8):11741-59. Epub 2014 Aug 7.

LCAE-URAC18, Faculté des Sciences, Université Mohammed Premier, B.P. 717, Oujda-60000, Morocco.

In view of the emerging importance of the ILs as "green" materials with wide applications and our general interests in green processes, a series of a twenty five new 1-alkyl-3-(4-phenoxybutyl) imidazolium-based ionic liquids (ILs) derivatives is synthesized using a facile and green ultrasound-assisted procedure. Their structures were characterized by FT-IR, 1H-NMR, 13C-NMR, 11B, 19F, 31P, and mass spectrometry. Antimicrobial screens of some selected ILs were conducted against a panel of Gram-positive and Gram-negative bacteria. The antimicrobial activity of each compound was measured by determination of the minimal inhibitory concentration (MIC) yielding very interesting and promising results. Their antibacterial activities are reported, and, on the basis of the experimental and virtual POM screening data available, attempt is also made to elucidate the structure activity relationship.
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http://dx.doi.org/10.3390/molecules190811741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270970PMC
August 2014

Synthesis of bis-acyclonucleoside analogues bearing benzothienyl-1,2,4-Triazol-3-Yl-disulfide under conventional and microwave methods.

Nucleosides Nucleotides Nucleic Acids 2013 ;32(1):28-41

Department of Chemistry, Taibah University, Madinah, Saudi Arabia.

The oxidation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol (1) with a solution of iodine and potassium iodide at room temperature afforded [5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-yl]disulfide (2). In contrast, when the reaction mixture was heated or irradiated by MW, an unexpected additional product was obtained and identified as 3-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole (3); the ratio of products was 3:1. The preferred conformer of 2 was deduced from the theoretical calculation. The alkylation of compounds 2 and 3 with epichlorohydrin and hydroxyalkylating agents gave the corresponding N,N-bis- and N-acyclonucleosides analogues 8-15.
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http://dx.doi.org/10.1080/15257770.2012.751491DOI Listing
July 2013

Revisit to the reaction of o-phenylene diamine with thiosemicarbazide to give benzimidazole-2-thione rather than benzotriazine-2-thione and its glycosylation.

Nucleosides Nucleotides Nucleic Acids 2010 Sep;29(9):698-706

International Center for Chemical and Biological Science, H E J Research Institute of Chemistry, University of Karachi, Karachi, Pakistan.

Reaction of o-phenylene diamine with thiosemicarbazide did not give benzotriazine-2-thione 2 as reported, although the product was found to be benzimidazole-2-thione 3. Glycosylation of 3 with acetobromo sugars 4a-4b gave the respective thioglycosides 7a-7d in addition to minor products of the nucleosides 8a and 8b, in the case of the gluco- and galacto-analogs, respectively. The regioselectivity of glycosylation reaction has been investigated.
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http://dx.doi.org/10.1080/15257770.2010.501777DOI Listing
September 2010

Regioselectivity in the glycosylation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol.

Carbohydr Res 2009 Apr 5;344(6):725-33. Epub 2009 Feb 5.

Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.

The glycosylation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol (1) and its 3-benzylsulfanyl and 3-methylsulfanyl derivatives with different glycosyl halides 2-4 has been studied in presence of base. The S-glycosides 5-7 were obtained in the presence of triethylamine, whereas the respective S,N(4)-bis(glycosyl) derivatives 8-10 were synthesized in the presence of potassium carbonate; the S,N(2)-bis(glycosyl) isomer 11 could also be isolated in the case of the galactosyl analog. Similarly, after protecting 1 as 3-benzyl(methyl)sulfanyl derivatives 12 or 13, the N(4)-glycosyl analogs 14-19 as well as minor amounts of S,N(2)-bis(galactosyl) isomers 20 and 21 were formed. The theoretical calculations using AM1 semiempirical methods agreed with the experimental results. Microwave irradiation (MWI) led to higher yields in much less time than the conventional methods, and no change in regioselectivity has been noticed.
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http://dx.doi.org/10.1016/j.carres.2009.01.026DOI Listing
April 2009