Publications by authors named "Mohammed F El-Behairy"

7 Publications

  • Page 1 of 1

Discovery of 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids as novel PPARα agonists with anti-hyperlipidemic and antioxidant activities: Design, synthesis and in vitro/in vivo biological evaluation.

Bioorg Chem 2021 Jul 16;115:105170. Epub 2021 Jul 16.

Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Cairo 12622, Egypt. Electronic address:

In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPARα agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPARα agonistic activity showing E% values of 50.80 and 90.55%, respectively, and EC values of 8.9 and 25.0 μM, respectively, compared to fenofibric acid with E = 100% and EC = 23.22 μM, respectively. These two compounds also stimulated carnitine palmitoyltransferase 1A gene transcription in HepG2 cells and PPARα protein expression. Molecular docking simulations were performed for the newly synthesized compounds to study their predicted binding pattern and energies in PPARα active site to rationalize their promising activity. In vivo, compounds 10a and 10i elicited a significant hypolipidemic activity improving the lipid profile in triton WR-1339-induced hyperlipidemic rats, including serum triglycerides, total cholesterol, LDL, HDL and VLDL levels. Compound 10i possessed better anti-hyperlipidemic activity than 10a. At a dose of 200 mg/kg, it demonstrated significantly lower TC, TG, LDL and VLDL levels than that of fenofibrate at the same dose with similar HDL levels. Compounds 10i and 10a possessed atherogenic indices (CRR, AC, AI, CRI-II) like that of fenofibrate. Additionally, a promising antioxidant activity indicated by the increased tissue reduced glutathione and plasma total antioxidant capacity with decreased plasma malondialdehyde levels was demonstrated by compounds 10a and 10i. No histopathological alterations were recorded in the hepatic tissue of compound 10i (200 mg/kg).
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http://dx.doi.org/10.1016/j.bioorg.2021.105170DOI Listing
July 2021

New Adenosine Derivatives from L.: In Vitro Anticholinesterase, Antimicrobial, and Cytotoxic Evaluation of Its Extracts.

Molecules 2021 Feb 24;26(5). Epub 2021 Feb 24.

Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat 32897, Egypt.

Aizoaceae is a large succulent family characterized by many psychoactive species. L., a wild neglected plant traditionally used in gastrointestinal ailments, has been the subject of a limited number of phytochemical and biological studies. Therefore, herein, we investigated the in vitro cytotoxic, antimicrobial, and anticholinesteraseactivity of the aerial parts of L. and analyzed the phytochemical compositions of the lipoidal and alkaloidal fractions. Petroleum ether extract showed the presence of behenic and tricosylic acid, while an in-depth investigation of the alkaloidal fraction revealed the identification of new adenine based alkaloids (1-5), which were isolated and identified for the first time from L. Their structures were elucidated based on extensive spectroscopic analyses. The alkaloidal extract showed a powerful cytotoxic effect (IC 14-28 μg/mL), with the best effect against colon carcinoma, followed by liver and breast carcinomas. The alkaloidal extract also had a potent effect against and , with minimum inhibitory concentrations (MIC) values of 312.5 and 625 µg/mL. The in vitro anticholinesterase activity was potent, with IC < 200 ng/mL for the tested extracts compared with 27.29 ± 0.49 ng/mL for tacrine.
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http://dx.doi.org/10.3390/molecules26051198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956659PMC
February 2021

Design, synthesis and antibacterial potential of 5-(benzo[d][1,3]dioxol-5-yl)-3-tert-butyl-1-substituted-4,5-dihydropyrazoles.

Saudi Pharm J 2015 Apr 28;23(2):202-9. Epub 2014 Jul 28.

Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, 12622 Dokki, Giza, Egypt.

A series of 5-(benzo[d][1,3]dioxol-5-yl)-3-tert-butyl-1-substituted-4,5-dihydropyrazole derivatives 4a-e and 6a-g have been synthesized and spectrally characterized. The antibacterial activity of the novel candidates has been screened using the agar diffusion test. These compounds were endowed with high antibacterial activity against different Gram +ve and Gram -ve bacteria when compared with standard antibacterial drugs. In the light of zone of inhibition and MIC results, Sarcina and Staphylococcus aureus are the most sensitive bacteria where pyrrolidinomethanone derivative 4e showed MICs at 80 and 110 nM, respectively. While hydroxypiperidinoethanone derivative 6c showed MIC at 90 nM for Sarcina.
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http://dx.doi.org/10.1016/j.jsps.2014.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421084PMC
April 2015

(E)-1-(1,3-Benzodioxol-5-yl)-4,4-di-methyl-pent-1-en-3-one.

Acta Crystallogr Sect E Struct Rep Online 2012 Mar 10;68(Pt 3):o634. Epub 2012 Feb 10.

In the mol-ecule of the title compound, C(14)H(16)O(3), all non-H atoms except for one methyl C atom lie on a crystallographic mirror plane. The conformation with respect to the C=C bond [1.3465 (12) Å] is trans. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds into C(5) chains propagating along [100].
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http://dx.doi.org/10.1107/S1600536812004242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295428PMC
March 2012

Design and synthesis of novel stiripentol analogues as potential anticonvulsants.

Eur J Med Chem 2012 Jan 11;47(1):360-9. Epub 2011 Nov 11.

Medicinal and Pharmaceutical Chemistry Department (Medicinal Chemistry group), Pharmaceutical and Drug Industries Research Division, National Research Centre, 12622 Dokki, Giza, Egypt.

A series of stiripentol (STP) analogues namely, 2-[(1E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ylidene]-N-(aryl/H)hydrazinecarboxamides 7a-h, (±)-(5RS)-N-(aryl/H)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazole-1-carboxamides (±)-8a-h, and (±)-[(5RS)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazol-1-yl](aryl)methanones (±)-13a-f was synthesized by adopting appropriate synthetic routes and was pharmacologically evaluated in the preliminary anticonvulsant screens. The selected bioactive new chemical entities were subjected to ED(50) determination and neurotoxicity evaluation. The most active congeners are 7h in MES screen and (±)-13b in scPTZ screen which displayed ED(50) values of 87 and 110 mg/kg, respectively, as compared to that of STP (ED(50) = 277.7 and 115 mg/kg in MES and scPTZ, respectively).
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http://dx.doi.org/10.1016/j.ejmech.2011.11.004DOI Listing
January 2012

Lipase-mediated enantioselective kinetic resolution of racemic acidic drugs in non-standard organic solvents: Direct chiral liquid chromatography monitoring and accurate determination of the enantiomeric excesses.

J Chromatogr A 2010 Feb 31;1217(7):1063-74. Epub 2009 Oct 31.

Australian Centre for Research on Separation Science, School of Chemistry, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia.

The enantioselective resolution of a set of racemic acidic compounds such as non-steroidal anti-inflammatory drugs (NSAIDs) of the group arylpropionic acid derivatives is demonstrated. Thus, a set of lipases were screened and manipulated in either the esterification or hydrolysis mode for the enantioselective kinetic resolution of these racemates in non-standard organic solvents. The accurate determination of the enantiomeric excesses of both substrate and product during such reaction is demonstrated. This was based on the development of a direct and reliable enantioselective high performance liquid chromatography (HPLC) procedure for the simultaneous baseline separation of both substrate and product in one run without derivatization. This was achieved using the immobilized chiral stationary phase namely Chiralpak IB, a 3,5-dimethylphenylcarbamate derivative of cellulose (the immobilized version of Chiralcel OD) which proved to be versatile for the monitoring of the lipase-catalyzed kinetic resolution of racemates in non-standard organic solvents.
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http://dx.doi.org/10.1016/j.chroma.2009.10.080DOI Listing
February 2010

Direct enantioselective HPLC monitoring of lipase-catalyzed kinetic resolution of tiaprofenic acid in nonstandard HPLC organic solvents.

Chirality 2008 Aug;20(8):871-7

Biomedicinal Chemistry Unit, Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

The first straightforward lipase-catalyzed enantioselective access to enantiomerically enriched tiaprofenic acid as a versatile method in chiral separation of racemates is demonstrated. The latter was directly monitored by enantioselective HPLC using a 3,5-dimethylphenylcarbamate derivative of cellulose-based chiral stationary phase namely Chiralpak IB (the immobilized version of Chiralcel OD). Non-standard HPLC organic solvents were used as diluent to dissolve the "difficult to dissolve" enzyme substrate (the acid) and as eluent for the simultaneous enantioselective HPLC baseline separation of both substrate and product in one run without any further derivatization. The existence of a non-standard HPLC organic solvent (e.g., methyl tert-butyl ether) in the mobile phase composition is mandatory to accomplish the simultaneous enantioselective HPLC baseline separation of both substrate and product.
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http://dx.doi.org/10.1002/chir.20533DOI Listing
August 2008
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