Mohamed Elagawany - Academia.edu (original) (raw)
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Papers by Mohamed Elagawany
RSC Advances
Versatile synthesis of benzotriazolyl alkyl esters (BAEs) from N-acylbenzotriazoles using DCM as ... more Versatile synthesis of benzotriazolyl alkyl esters (BAEs) from N-acylbenzotriazoles using DCM as a methylene building block.
Tetrahedron Letters, 2016
Chemical Biology & Drug Design, 2016
A set of diphenyl ether derivatives bearing different heterocycles were synthesized from 4-phenox... more A set of diphenyl ether derivatives bearing different heterocycles were synthesized from 4-phenoxybenzohydrazide 1 in good yield. Synthesized compounds were screened against a broad panel of viruses in different cell cultures and some of the compounds showed promising antiviral properties. This article is protected by copyright. All rights reserved.
Green Chemistry Letters and Reviews, 2016
Synthesis, Oct 9, 2012
ABSTRACT Several synthetic strategies were developed for the preparation of highly substituted py... more ABSTRACT Several synthetic strategies were developed for the preparation of highly substituted pyrido[2,3-d]pyridazines. We particularly focused on the impact of the pyridine nitrogen atom on pyridazine ring reactivity toward aromatic substitutions, alkylations, or pallado-catalyzed cross-coupling reactions.
Journal of Biosciences and Medicines, 2015
Tetrahedron Letters, 2007
A simple and efficient methodology for regioselective alkylation of exocyclic nitrogen of cyclic ... more A simple and efficient methodology for regioselective alkylation of exocyclic nitrogen of cyclic amidines was developed by microwave-assisted heating in the presence of amines. Novel N-alkylated 3,4-dihydropyrazino[2,1-b]quinazolin-6-ones were prepared in good yields. The reaction occurred via a transamination (addition-elimination) process involving a first attack of the amine on the electrophilic carbon of the amidine function.
Arkivoc, 2014
Unprotected O-acylated serine and O-acylated threonine isopeptides have been synthesized, and the... more Unprotected O-acylated serine and O-acylated threonine isopeptides have been synthesized, and their conversion to native tripeptides and tetrapeptides by O-to N-terminus transfer investigated. Ligations involving 8-and 11-membered cyclic transition states are shown experimentally and computationally to be more favorable than intermolecular cross-ligations. transition state resulting in the native peptide bond. The bifunctional nature of the N-terminal cysteine 1,2-mercaptoamine moiety is responsible for the observed chemoselectivity in NCL. 14 NCL development as a synthetic tool for building peptides depends on additives to increase ligation rates and yields. Ligations depend on factors such as steric demand, the exogenous thiol reactivity and the nature of the solvent. 14-17 In addition, the low abundance of cysteine (1.7% of the residues in protein sequences) is a major drawback of this methodology since NCL is restricted to Cys residues.
Organic & biomolecular chemistry, Jan 10, 2015
Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole ... more Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.
ChemInform, 2013
ABSTRACT The work features solution phase benzotriazole-mediated peptide synthesis ligating nativ... more ABSTRACT The work features solution phase benzotriazole-mediated peptide synthesis ligating native amino acids.
Organic & Biomolecular Chemistry, 2012
Chemical ligation via Oto N-acyl transfer of O-acylated serine containing peptides affords serine... more Chemical ligation via Oto N-acyl transfer of O-acylated serine containing peptides affords serine containing native peptides via 8-and 11-membered cyclic transition states opening the door to a wide variety of potential applications to peptide elaboration. The feasibility of these traceless chemical ligations is feasible as supported by computation. † Electronic supplementary information (ESI) available: 1 H and 13 C NMR for all compounds and HPLC/Mass-Spectrometry spectra for compounds 4, 5, 7 and 8. See Scheme 1 Preparation of O-acyl isodipeptides 4a-c. Scheme 2 Chemical ligation of O-acyl isodipeptides 4a,c. Scheme 3 Preparation of O-acyl isotripeptides 7a-b and their ligation to 8a-b.
Bioorganic & Medicinal Chemistry Letters, 2013
The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synth... more The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors.
Anti-Cancer Agents in Medicinal Chemistry, 2013
Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combreta... more Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDAMB- 435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.
Angewandte Chemie International Edition, 1999
Amino acids and their derivatives are unequivocally one of the most important classes of organic ... more Amino acids and their derivatives are unequivocally one of the most important classes of organic compounds. In addition to biochemical applications, amino acid derivatives are used as chemical feedstocks for industrial fine chemical synthesis. Despite the well known ªclassical methodsº such as the Strecker synthesis [2] and the highly selective procedures developed in the research groups of Schöllkopf, [3] Seebach, [4] Evans, [5] Williams as well as recent developments, [7] a need for new, more efficient protocols for the preparation of amino acid derivatives remains. In the past, researchers focused exclusively on the asymmetric synthesis of amino acid derivatives, and successful procedures were judged accordingly. However, other important factors also need to be addressed. For example, the procedures need to be improved in terms of their atom economy. [8] This also applies to the asymmetric hydrogenation of acetamidoacrylates and acetamidocinnamates, [9] since the hydrogenation precursors are often expensive and difficult to prepare. Racemic imidazolidine-2,4-diones, generally called hydantoins, are important building blocks for enantioselective amino acid synthesis because enantiomerically pure amino acids can be prepared from these by dynamic kinetic racemic resolution. The practicability of this method was demonstrated on an industrial scale by Ajinomoto and Kanegafuchi for the production of d-p-hydroxyphenylglycine. Substituted hydantoins are also of pharmacological interest and are used, for example, for the treatment of epilepsy .
RSC Advances
Versatile synthesis of benzotriazolyl alkyl esters (BAEs) from N-acylbenzotriazoles using DCM as ... more Versatile synthesis of benzotriazolyl alkyl esters (BAEs) from N-acylbenzotriazoles using DCM as a methylene building block.
Tetrahedron Letters, 2016
Chemical Biology & Drug Design, 2016
A set of diphenyl ether derivatives bearing different heterocycles were synthesized from 4-phenox... more A set of diphenyl ether derivatives bearing different heterocycles were synthesized from 4-phenoxybenzohydrazide 1 in good yield. Synthesized compounds were screened against a broad panel of viruses in different cell cultures and some of the compounds showed promising antiviral properties. This article is protected by copyright. All rights reserved.
Green Chemistry Letters and Reviews, 2016
Synthesis, Oct 9, 2012
ABSTRACT Several synthetic strategies were developed for the preparation of highly substituted py... more ABSTRACT Several synthetic strategies were developed for the preparation of highly substituted pyrido[2,3-d]pyridazines. We particularly focused on the impact of the pyridine nitrogen atom on pyridazine ring reactivity toward aromatic substitutions, alkylations, or pallado-catalyzed cross-coupling reactions.
Journal of Biosciences and Medicines, 2015
Tetrahedron Letters, 2007
A simple and efficient methodology for regioselective alkylation of exocyclic nitrogen of cyclic ... more A simple and efficient methodology for regioselective alkylation of exocyclic nitrogen of cyclic amidines was developed by microwave-assisted heating in the presence of amines. Novel N-alkylated 3,4-dihydropyrazino[2,1-b]quinazolin-6-ones were prepared in good yields. The reaction occurred via a transamination (addition-elimination) process involving a first attack of the amine on the electrophilic carbon of the amidine function.
Arkivoc, 2014
Unprotected O-acylated serine and O-acylated threonine isopeptides have been synthesized, and the... more Unprotected O-acylated serine and O-acylated threonine isopeptides have been synthesized, and their conversion to native tripeptides and tetrapeptides by O-to N-terminus transfer investigated. Ligations involving 8-and 11-membered cyclic transition states are shown experimentally and computationally to be more favorable than intermolecular cross-ligations. transition state resulting in the native peptide bond. The bifunctional nature of the N-terminal cysteine 1,2-mercaptoamine moiety is responsible for the observed chemoselectivity in NCL. 14 NCL development as a synthetic tool for building peptides depends on additives to increase ligation rates and yields. Ligations depend on factors such as steric demand, the exogenous thiol reactivity and the nature of the solvent. 14-17 In addition, the low abundance of cysteine (1.7% of the residues in protein sequences) is a major drawback of this methodology since NCL is restricted to Cys residues.
Organic & biomolecular chemistry, Jan 10, 2015
Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole ... more Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.
ChemInform, 2013
ABSTRACT The work features solution phase benzotriazole-mediated peptide synthesis ligating nativ... more ABSTRACT The work features solution phase benzotriazole-mediated peptide synthesis ligating native amino acids.
Organic & Biomolecular Chemistry, 2012
Chemical ligation via Oto N-acyl transfer of O-acylated serine containing peptides affords serine... more Chemical ligation via Oto N-acyl transfer of O-acylated serine containing peptides affords serine containing native peptides via 8-and 11-membered cyclic transition states opening the door to a wide variety of potential applications to peptide elaboration. The feasibility of these traceless chemical ligations is feasible as supported by computation. † Electronic supplementary information (ESI) available: 1 H and 13 C NMR for all compounds and HPLC/Mass-Spectrometry spectra for compounds 4, 5, 7 and 8. See Scheme 1 Preparation of O-acyl isodipeptides 4a-c. Scheme 2 Chemical ligation of O-acyl isodipeptides 4a,c. Scheme 3 Preparation of O-acyl isotripeptides 7a-b and their ligation to 8a-b.
Bioorganic & Medicinal Chemistry Letters, 2013
The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synth... more The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors.
Anti-Cancer Agents in Medicinal Chemistry, 2013
Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combreta... more Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDAMB- 435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.
Angewandte Chemie International Edition, 1999
Amino acids and their derivatives are unequivocally one of the most important classes of organic ... more Amino acids and their derivatives are unequivocally one of the most important classes of organic compounds. In addition to biochemical applications, amino acid derivatives are used as chemical feedstocks for industrial fine chemical synthesis. Despite the well known ªclassical methodsº such as the Strecker synthesis [2] and the highly selective procedures developed in the research groups of Schöllkopf, [3] Seebach, [4] Evans, [5] Williams as well as recent developments, [7] a need for new, more efficient protocols for the preparation of amino acid derivatives remains. In the past, researchers focused exclusively on the asymmetric synthesis of amino acid derivatives, and successful procedures were judged accordingly. However, other important factors also need to be addressed. For example, the procedures need to be improved in terms of their atom economy. [8] This also applies to the asymmetric hydrogenation of acetamidoacrylates and acetamidocinnamates, [9] since the hydrogenation precursors are often expensive and difficult to prepare. Racemic imidazolidine-2,4-diones, generally called hydantoins, are important building blocks for enantioselective amino acid synthesis because enantiomerically pure amino acids can be prepared from these by dynamic kinetic racemic resolution. The practicability of this method was demonstrated on an industrial scale by Ajinomoto and Kanegafuchi for the production of d-p-hydroxyphenylglycine. Substituted hydantoins are also of pharmacological interest and are used, for example, for the treatment of epilepsy .