Publications by authors named "Khalid Bougrin"

21 Publications

  • Page 1 of 1

Biological, toxicological and molecular docking evaluations of isoxazoline-thiazolidine-2,4-dione analogues as new class of anti-hyperglycemic agents.

J Biomol Struct Dyn 2021 Dec 26:1-13. Epub 2021 Dec 26.

Laboratory of Pharmacology and Toxicology, Biopharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.

In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, H-NMR, C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC= 97.12 ± 0.35 µM and IC= 2.97 ± 0.01 μM). All compounds were then evaluated for their acute toxicity and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.2017348DOI Listing
December 2021

Ultrasound-assisted one-pot three-component synthesis of new isoxazolines bearing sulfonamides and their evaluation against hematological malignancies.

Ultrason Sonochem 2021 Oct 9;78:105748. Epub 2021 Sep 9.

Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculty of Science, B.P. 1014, Geophysics, Natural Patrimony and Green Chemistry (GEOPAC) Research Center, Mohammed V University in Rabat, Morocco; Chemical & Biochemical Sciences Green-Process Engineering (CBS) Mohammed VI Polytechnic University, Lot 660, Hay Moulay Rachid, Benguerir, Morocco. Electronic address:

In the present study, following a one-pot two-step protocol, we have synthesized novel sulfonamides-isoxazolines hybrids (3a-r) via a highly regioselective 1,3-dipolar cycloaddition. The present methodology capitalized on trichloroisocyanuric acid (TCCA) as a safe and ecological oxidant and chlorinating agent for the in-situ conversion of aldehydes to nitrile oxides in the presence of hydroxylamine hydrochloride, under ultrasound activation. These nitrile oxides could be engaged in 1,3-dipolar cycloaddition reactions with various alkene to afford the targeted sulfonamides-isoxazolines hybrids (3a-r). The latter were assessed for their antineoplastic activity against model leukemia cell lines (Chronic Myeloid Leukemia, K562 and Promyelocytic Leukemia, HL-60).
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http://dx.doi.org/10.1016/j.ultsonch.2021.105748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436160PMC
October 2021

Synthesis, α-glucosidase and α-amylase inhibitory activities, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives.

J Biomol Struct Dyn 2021 Apr 13:1-12. Epub 2021 Apr 13.

Laboratory of Pharmacology and Toxicology, Biopharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.

In the present study, a series of thiazolidine-2,4-diones derivatives () and () were synthesized and characterized by H NMR, C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. biological investigations revealed that most of compounds were active against α-glucosidase with IC values in the range of 43.85 ± 1.06 to 380.10 ± 1.02 µM, and α-amylase with IC in the range of 18.19 ± 0.11 to 208.10 ± 1.80 µM. Some of the tested compounds were found to be more potent inhibitors than the clinical drug Acarbose (IC = 97.12 ± 0.35 µM and IC = 2.97 ± 0.004 μM). The lead compounds were evaluated for their acute toxicity on Swiss mice and found to be completely non-toxic with LD > 2000 mg/kg BW. Furthermore, the Structure-activity relationship (SAR) and the binding interactions of all compounds with the active site of α-glucosidase and α-amylase were confirmed through molecular docking and stabilizing energy calculations. This study has identified the inhibitory potential a new class of synthesized thiazolidine-2,4-diones in controlling both hyperglycemia and type 2 diabetes mellitus. Furthermore, the theoretical binding mode of the target molecules was evaluated by molecular docking studies against the 3D Crystal Structure of human pancreatic α-amylase (PDB ID: 1B2Y) and α-glucosidase (PDB ID: 3W37)Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1911854DOI Listing
April 2021

5-((1H-imidazol-1-yl)methyl)quinolin-8-ol as potential antiviral SARS-CoV-2 candidate: Synthesis, crystal structure, Hirshfeld surface analysis, DFT and molecular docking studies.

J Mol Struct 2021 May 27;1232:130005. Epub 2021 Jan 27.

Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique-URAC23, GEOPAC, Département de Chimie, Faculté des Sciences, Université Mohammed V in Rabat, Morocco.

A potential new drug to treat SARS-CoV-2 infections and chloroquine analogue, 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol () has been here synthesized and characterized by FT-IR, H-NMR, C-NMR, ultraviolet-visible, ESI-MS and single-crystal X-ray diffraction. was optimized in gas phase, aqueous and DMSO solutions using hybrid B3LYP/6-311++G(d,p) method. Comparisons between experimental and theoretical infrared spectra, H and C NMR chemical shifts and electronic spectrum in DMSO solution evidence good concordances. Higher solvation energy was observed in aqueous solution than in DMSO, showing in aqueous solution a higher value than antiviral brincidofovir and chloroquine. on Bond orders, atomic charges and topological studies suggest that imidazole ring play a very important role in the properties of . NBO and AIM analyses support the intra-molecular O15-H16•••N17 bonds of in the three media. Low gap value supports the higher reactivity of DD1 than chloroquine justified by the higher electrophilicity and low nucleophilicity. Complete vibrational assignments of in gas phase and aqueous solution are reported together with the scaled force constants. In addition, better intermolecular interactions were observed by Hirshfeld surface analysis. Finally, the molecular docking mechanism between ligand and COVID-19/6WCF and COVID-19/6Y84 receptors were studied to explore the binding modes of these compounds at the active sites. Molecular docking results have shown that the molecule can be considered as a potential agent against COVID-19/6Y84-6WCF receptors.
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http://dx.doi.org/10.1016/j.molstruc.2021.130005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839438PMC
May 2021

Ultrasound-assisted one-pot green synthesis of new N- substituted-5-arylidene-thiazolidine-2,4-dione-isoxazoline derivatives using NaCl/Oxone/NaPO in aqueous media.

Ultrason Sonochem 2020 Nov 15;68:105222. Epub 2020 Jun 15.

Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculty of Science, B.P. 1014, Geophysics, Natural Patrimony and Green Chemistry (GEOPAC) Research Center, Mohammed V University of Rabat, Morocco; Mohammed VI Polytechnic University, Lot 660, Hay Moulay Rachid, Benguerir, Morocco. Electronic address:

A rapid and green method for the synthesis of novel N-thiazolidine-2,4-dione isoxazoline derivatives 5 from N-allyl-5-arylidenethiazolidine-2,4-diones 3 as dipolarophiles with arylnitrile oxides via 1,3-dipolar cycloaddition reaction. The corresponding N-allyl substituted dipolarophiles were prepared by one-pot method from thiazolidine-2,4-dione with aldehydes using Knoevenagel condensation followed by N-allylation of thiazolidine-2,4-dione in NaOH aqueous solution under sonication. In addition, the isoxazoline derivatives 5 were synthesized by regioselective and chemoselective 1,3-dipolar cycloaddition using inexpensive and mild NaCl/Oxone/NaPO as a Cl source, oxidant and/or catalyst under ultrasonic irradiation in EtOH/HO (v/v, 2:1) as green solvent. All synthesized products are furnished in good yields in the short reaction time, and then their structures were confirmed by NMR, mass spectrometry and X-ray crystallography analysis.
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http://dx.doi.org/10.1016/j.ultsonch.2020.105222DOI Listing
November 2020

Concise synthesis and antibacterial evaluation of novel 3-(1,4-disubstituted-1,2,3-triazolyl)uridine nucleosides.

Arch Pharm (Weinheim) 2018 Nov 1;351(11):e1800204. Epub 2018 Oct 1.

Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique, Faculty of Science, Geophysics, Natural Patrimony and Green Chemistry (GEOPAC) Research Center, Mohammed V University in Rabat, Rabat, Morocco.

We report herein a simple and efficient synthesis of a new series of antibacterial uridine nucleosides. The strategy involved a sequential silylation/N-glycosylation/N-propargylation procedure of uracil 1 for preparing the dipolarophile 5 in good yield. A series of novel uridine-[1,2,3]triazole nucleosides 6a-j were efficiently synthesized via the copper-catalyzed azide-alkyne cycloaddition (CuAAC) from dipolarophile 5 with different selected azides. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvements were observed when reactions were carried out under sonication. Their antibacterial potential has been evaluated by means of a micro-dilution assay against either Gram-positive or Gram-negative bacteria. Compounds 6i and 6j have shown significant bactericidal activity against Staphylococcus aureus (MIC = 10 and 6 μM, respectively), and 6h against Escherichia coli (MIC = 8 μM). Moreover, antibacterial kinetic assays showed that 6i and 6j significantly reduced the S. aureus growth rate at the MIC concentration, after 6 h, compared to their deprotected analogs, 6k and 6l, respectively. Compound 6h also significantly reduced the growth of E. coli. These antibacterial effects may be related to the penetrating properties of these compounds, as revealed by the leakage of nucleic acids from the sensitive strains.
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http://dx.doi.org/10.1002/ardp.201800204DOI Listing
November 2018

Modular synthesis of new C-aryl-nucleosides and their anti-CML activity.

Bioorg Med Chem Lett 2018 06 24;28(10):1931-1936. Epub 2018 Mar 24.

Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR 7272, 06108 Nice, France; Mohamed VI Polytechnic University, UM6P, 43150 Ben Guerir, Morocco. Electronic address:

The C-aryl-ribosyles are of utmost interest for the development of antiviral and anticancer agents. Even if several synthetic pathways have been disclosed for the preparation of these nucleosides, a direct, few steps and modular approaches are still lacking. In line with our previous efforts, we report herein a one step - eco-friendly β-ribosylation of aryles and heteroaryles through a direct Friedel-Craft ribosylation mediated by bismuth triflate, Bi(OTf). The resulting carbohydrates have been functionalized by cross-coupling reactions, leading to a series of new C-aryl-nucleosides (32 compounds). Among them, we observed that 5d exerts promising anti-proliferative effects against two human Chronic Myeloid Leukemia (CML) cell lines, both sensitive (K562-S) or resistant (K562-R) to imatinib, the "gold standard of care" used in this pathology. Moreover, we demonstrated that 5d kills CML cells by a non-conventional mechanism of cell death.
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http://dx.doi.org/10.1016/j.bmcl.2018.03.063DOI Listing
June 2018

Ultrasound-assisted facile one-pot sequential synthesis of novel sulfonamide-isoxazoles using cerium (IV) ammonium nitrate (CAN) as an efficient oxidant in aqueous medium.

Ultrason Sonochem 2018 Jan 11;40(Pt A):289-297. Epub 2017 Jul 11.

Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Université Mohammed V, Faculté des Sciences, B.P. 1014 Rabat, Morocco. Electronic address:

A series of novel 3,5-disubstituted isoxazoles have been synthesized, using a new, green, and versatile "one-pot three-steps" methodology. The key step is an oxidative 1,3-dipolar cycloaddition under ultrasonic irradiation, occurring in aqueous media, and mediated by cerium (IV) ammonium nitrate (CAN). CAN is a one-electron oxidant, highly soluble in water, slightly toxic and inexpensive, that allows the in situ conversion of the intermediate aldoximes into nitrile oxide. The syntheses are highly regioselective, as illustrated by the structures of the final compounds, which have been fully assessed by spectral analyses (H and C NMR, MS). This study illustrates the potency of the ultrasound activation to synthesize a set of highly functionalized heterocycles, with potential applications in biology, in short reaction times and following an eco-friendly process.
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http://dx.doi.org/10.1016/j.ultsonch.2017.07.019DOI Listing
January 2018

Synthesis and anti-cancer activities of new sulfonamides 4-substituted-triazolyl nucleosides.

Bioorg Med Chem Lett 2017 05 9;27(9):1989-1992. Epub 2017 Mar 9.

Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR 7272, 06108 Nice, France. Electronic address:

Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market. To improve the activity of AICAR, we report herein an efficient synthesis of new series of sulfonamide-4-substituted-1,2,3-triazolyl nucleosides using a Cu-catalyzed 1,3-dipolar cycloaddition. All these molecules have been fully characterized and evaluated against two aggressive tumor cell lines, RCC4 and MDA-MB-231. Among them, nucleoside analogue 5i belonging to the ribose series was found to be 19 to 66-fold more active than AICAR. Western blot analyses on RCC4 cells showed that 5i displayed an interesting mode of action by inducing both apoptosis and autophagy cell death, making therefore this class of molecules highly promising for further hit-to-lead optimization.
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http://dx.doi.org/10.1016/j.bmcl.2017.03.018DOI Listing
May 2017

In Vitro and in Vivo Evaluation of Fully Substituted (5-(3-Ethoxy-3-oxopropynyl)-4-(ethoxycarbonyl)-1,2,3-triazolyl-glycosides as Original Nucleoside Analogues to Circumvent Resistance in Myeloid Malignancies.

J Med Chem 2017 02 2;60(4):1523-1533. Epub 2017 Feb 2.

Institut de Chimie de Nice UMR7272, Université Côte d'Azur, CNRS , 06108 Nice, France.

A series of nucleoside analogues bearing a 1,4,5-trisubstituted-1,2,3-triazole aglycone was synthesized using a straightforward click/electrophilic addition or click/oxidative coupling tandem procedures. SAR analysis, using cell culture assays, led to the discovery of a series of compounds belonging to the 5-alkynyl-1,2,3-triazole family that exhibits potent antileukemic effects on several hematologic malignancies including chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) either sensitive or resistant to their respective therapy. Compound 4a also proved efficient in vivo on mice xenografted with SKM1-R MDS cell line. Additionally, some insights in its mode of action revealed that this compound induced cell death by caspase and autophagy induction.
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http://dx.doi.org/10.1021/acs.jmedchem.6b01803DOI Listing
February 2017

Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives.

Molecules 2016 Aug 9;21(8). Epub 2016 Aug 9.

Institut de Chimie de Nice, ICN UMR UNS CNRS 7272, Université Nice-Sophia Antipolis-Université Côte d'Azur, Parc Valrose, 06108 Nice Cedex 2, France.

This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc. Green syntheses and solvent-free procedures have been introduced whenever possible. The syntheses discussed herein have been selected to illustrate the huge potential of microwave in the synthesis of highly functionalized molecules with potential therapeutic applications, in high yields, enhanced reaction rates and increased chemoselectivity, compared to conventional methods. More than 100 references from the recent literature are listed in this review.
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http://dx.doi.org/10.3390/molecules21081032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273266PMC
August 2016

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues.

Molecules 2016 Apr 14;21(4):492. Epub 2016 Apr 14.

Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculté des Sciences, Université Mohammed V, B.P. 1014 Rabat, Maroc.

This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed.
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http://dx.doi.org/10.3390/molecules21040492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273482PMC
April 2016

Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticancer agents.

Chem Biol 2014 Nov 16;21(11):1433-43. Epub 2014 Oct 16.

OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France. Electronic address:

The c-Jun N-terminal kinase (JNK) family, with its three members JNK1, JNK2, and JNK3, is a subfamily of mitogen-activated protein kinases. Involved in many aspects of cellular processes, JNK has been also associated with pathological states such as neurodegenerative diseases, inflammation, and cancers. In oncology, each isoform plays a distinct role depending on the context of the targeted tissue/organ, the tumor stage, and, most likely, the signaling pathway activated upstream. Consequently, the current challenge in finding new successful anti-JNK therapies is to design isoform-selective inhibitors of the JNKs. In this review, a particular focus is given to the JNK inhibitors that have been developed thus far when examining 3D structures of various JNK-inhibitor complexes. Using current data regarding structure-activity relationships and medicinal chemistry approaches, our objective is to provide a better understanding of the design and development of selective JNK inhibitors in the present and future.
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http://dx.doi.org/10.1016/j.chembiol.2014.09.007DOI Listing
November 2014

Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

Molecules 2014 Oct 10;19(10):16223-39. Epub 2014 Oct 10.

OriBase Pharma, Parc Euromedecine, Cap Gamma, 1682, rue de la Valsière, 34189 Montpellier, France.

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.
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http://dx.doi.org/10.3390/molecules191016223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271404PMC
October 2014

FeCl3-promoted and ultrasound-assisted synthesis of resveratrol O-derived glycoside analogs.

Ultrason Sonochem 2015 Jan 10;22:15-21. Epub 2014 Jun 10.

Institut de Chimie de Nice UMR CNRS 7272, Université Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France. Electronic address:

Phenol derived O-glycosides were synthesized using a direct and convenient O-glycosidation, starting from acetylated sugars in the presence of FeCl3, an inexpensive, mild and benign Lewis acid catalyst. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with conventional conditions leading to the corresponding β-O-glycosides as the major anomer. Post-synthetic transformations of iodophenol intermediates led to new resveratrol O-glycoside analogs in good overall yields.
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http://dx.doi.org/10.1016/j.ultsonch.2014.05.022DOI Listing
January 2015

Ultrasound-assisted one-pot synthesis of anti-CML nucleosides featuring 1,2,3-triazole nucleobase under iron-copper catalysis.

Ultrason Sonochem 2012 Nov 25;19(6):1132-8. Epub 2012 Apr 25.

Institut de Chimie de Nice UMR CNRS 7272, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.

A simple and efficient synthesis of modified 1,2,3-triazole nucleosides was developed. The strategy involved sequential one-pot acetylation-azidation-cycloaddition procedure and was found to be highly effective under a cooperative effect of ultrasound activation and iron/copper catalysis. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with conventional conditions. This one-pot procedure provides several advantages such as operational simplicity, high yield, safety and environment friendly protocol. The resulting substituted nucleosides were evaluated for their anticancer activity against K562 chronic myelogenous leukemia (CML) cell line.
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http://dx.doi.org/10.1016/j.ultsonch.2012.04.007DOI Listing
November 2012

Microwave-assisted and efficient solvent-free knoevenagel condensation. A sustainable protocol using porous calcium hydroxyapatite as catalyst.

Molecules 2010 Feb 4;15(2):813-23. Epub 2010 Feb 4.

Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, Université Mohammed V-Agdal, Faculté des Sciences, B.P. 1014 R.P, Rabat, Maroc.

A sustainable Knoevenagel condensation of a series of aldehydes with malononitrile and ethyl cyanoacetate is described. The process is based on the combination of microwave activation and hydroxyapatite catalysis under solvent-free conditions. Products are obtained in and high yields after short reaction times. The effects of the specific surface of porous calcium hydroxyapatite and microwave activation are discussed.
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http://dx.doi.org/10.3390/molecules15020813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257047PMC
February 2010

1-(3-p-Tolyl-isoxazol-5-yl)cyclo-hexa-nol.

Acta Crystallogr Sect E Struct Rep Online 2009 Nov 4;65(Pt 12):o2971. Epub 2009 Nov 4.

The title compound, C(16)H(19)NO(2), contains two mol-ecules in the asymmetric unit. Each mol-ecule is composed of three inter-connected rings, two essentially planar rings, viz. the isoxazole and the methyl-benzyl aromatic ring [maximum deviations of 0.0027 (13) and 0.0031 (19) Å from the isoxazole and methylbenzyl ring planes, respectively, in the first molecule, 0.0018 (12) and 0.019 (2) Å in the second molecule], and one cyclo-hexa-nol ring having a chair conformation. Although the two mol-ecules have similar bond distances and angles, they differ in the orientation of the cyclo-hexa-nol ring with respect to the tolyl-isoxazole unit. In the first mol-ecule, the dihedral angle between the isoxazole and methyl-benzyl rings is 22.03 (8)° and between the isoxazole and cyclo-hexa-nol rings is 30.15 (8)°. The corresponding values in the second mol-ecule are 6.13 (10) and 88.44 (8)°, respectively. In the crystal, the molecules are linked by O-H⋯O and O-H⋯N hydrogen bonds, building up a zigzag chain parallel to the a axis.
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http://dx.doi.org/10.1107/S1600536809044900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2972041PMC
November 2009

Efficient synthesis and in vitro cytostatic activity of 4-substituted triazolyl-nucleosides.

Bioorg Med Chem Lett 2007 Dec 29;17(23):6656-9. Epub 2007 Sep 29.

Laboratoire de Chimie des Molécules Bioactives et des Arômes, UMR-CNRS 6001, Institut de Chimie de Nice, Université de Nice-Sophia Antipolis, Parc Valrose, F-06108 Nice Cédex 2, France.

We report herein an efficient synthesis of 4-substituted triazolyl-nucleosides and their in vitro cytostatic activity. The synthesis is based on a straightforward 1,3-dipolar cycloaddition between 1-azido-ribose 2 and terminal alkynes under a cooperative effect of microwave activation and copper (I) catalysis. All cycloadducts were obtained in nearly quantitative yield after a short reaction time (1 to 2min). After removal of acetyl protecting groups, the free nucleosides were evaluated against L1210, Molt4/C8, and CEM tumor cell lines. Structure-activity relationship study shows that the substituent on the triazole ring has a major effect since nucleosides 4c and 4g, containing, respectively, a long alkyl chain and an aryl donor group are the most active compounds in this series.
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http://dx.doi.org/10.1016/j.bmcl.2007.08.077DOI Listing
December 2007

Enantioselective organocatalytic oxidation of functionalized sterically hindered disulfides.

Org Lett 2007 Mar 7;9(7):1255-8. Epub 2007 Mar 7.

Instituto de Investigaciones Químicas, C.S.I.C-Universidad de Sevilla, c/ Américo Vespucio, 49, Isla de la Cartuja, 41092 Sevilla, Spain.

[structure: see text]. The first study on enantioselective oxidation of functionalized sterically hindered disulfides is reported. This study shows that the Shi organocatalytic system using carbohydrate-derived ketone with oxone is superior to the Ellman-Bolm vanadium catalyst in terms of chemical yield and enantioselectivity. Whereas the latter system afforded mostly racemic thiosulfinates in low to moderate yields, the former one afforded thiosulfinates with up to 96% ee.
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http://dx.doi.org/10.1021/ol070056zDOI Listing
March 2007

Synthesis and studies of modified oligonucleotides-directed triple helix formation at the purine-pyrimidine interrupted site.

Nucleosides Nucleotides Nucleic Acids 2003 May-Aug;22(5-8):1277-80

Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, Universitè des Sciences, Rabat, Morocco.

Triple helix formation is still restricted to oligopurine-oligopyrimidine double stranded DNA target. Herein we focus on our progress achieved in nucleobase and oligonucleotide modifications area to address the chemical challenge to circumvent the recognition of a purine-pyrimidine base pair interruption in an oligopyrimidine-oligopurine DNA sequence.
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http://dx.doi.org/10.1081/NCN-120022945DOI Listing
December 2003
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