Publications by authors named "Mina Aadil"

3 Publications

  • Page 1 of 1

Synthesis and bioactivity of novel amino-pyrazolopyridines.

Eur J Med Chem 2014 Oct 5;85:450-7. Epub 2014 Aug 5.

Laboratoire de Chimie Bioorganique et Analytique (LCBA), Université Hassan II Mohammedia-Casablanca, FST-Mohammedia, BP 146, 20800 Mohammedia, Morocco. Electronic address:

Here we describe the synthesis and biological activity of novel amino-pyrazolopyridines with anti-NF-κB and pro-apoptotic potential. α-Methylene ketones were used as a starting point for synthesis of amino-pyrazolopyridine 3. The alkylidene malononitriles 1 were obtained by the Knoevenagel reaction of ketones with malononitriles. Vilsmeier-Haack reaction allowed direct access to 2-chloro-3-cyanopyridines 2. Those products, by refluxing with hydrazine hydrate, allowed cyclization to amino-pyrazolopyridines 3a-g, which were not previously described in the literature. Bioactivity results indicated that amino-pyrazolopyridines 3a, 3b and 3g induced apoptotic cell death in K562 cancer cells with an IC50 of 36.5 ± 3.9 μM, 27.6 ± 4.5 μM and 35.0 ± 2.3 μM, respectively, after 72 h. In addition, compounds 3a, 3b and 3g exerted NF-κB inhibition activity with an IC50 of 4.7 ± 1.6 μM, 6.9 ± 1.9 μM and 39.8 ± 3.9 μM, respectively, after 8 h in K562 cells activated with TNFα. Compounds 3b and 3g showed interesting differential toxicity as viability of peripheral blood mononuclear cells (PBMCs) from healthy donors remained largely unaffected by this treatment.
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http://dx.doi.org/10.1016/j.ejmech.2014.08.008DOI Listing
October 2014

Synthesis and optimization of an original V-shaped collection of 4-7-disubstituted pyrido[3,2-d]pyrimidines as CDK5 and DYRK1A inhibitors.

Eur J Med Chem 2014 Jun 22;80:352-63. Epub 2014 Apr 22.

Institut de Chimie Organique et Analytique, CNRS UMR 7311, B.P. 6759, 45067 Orléans Cedex 2, France. Electronic address:

We here report the synthesis and biological evaluation of an original collection of 4,7-disubstituted pyrido[3,2-d]pyrimidines designed as potential kinase inhibitors. The collection was generated from a single starting material, 4,7-dichloropyrido[3,2-d]pyrimidine, which afforded the final compounds after two steps: a sequential or one-pot sequence including selective cross coupling reactions in C-4, followed by the second cross-coupling in C-7. In position C-4, a Suzuki-Miyaura type reaction led to monosubstituted derivatives whereas in position C-7, synthesis was achieved via a Suzuki or a Buchwald type reaction using commercially available or undescribed boron derivatives. The biological activity of the V-shaped family was measured in protein kinase assays. The structure activity relationship (SAR) revealed that some compounds selectively inhibited DYRK1A and CDK5 without affecting GSK3. Docking studies furnished possible explanations that correlate with the SAR data. The most active compound on the two biological targets was 27 which exhibited the following IC50: 110 nM for CDK5, 24 nM for DYRK1A and only 1.2 μM for GSK3. In the C-7 amino subfamily, the best derivative was indubitably compound 48 which led to a near selective action on DYRK1A and a remarkable IC50 of 60 nM.
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http://dx.doi.org/10.1016/j.ejmech.2014.04.055DOI Listing
June 2014

Quantitative structure-diastereoselectivity relationships for arylsulfoxide derivatives in radical chemistry.

J Mol Model 2003 Aug 24;9(4):242-7. Epub 2003 May 24.

Laboratoire de Catalyse, Synthèse et Environnement, Département de Chimie, Faculté des Sciences et Techniques, UFR Chimie Appliquée, B.P. 146, 20650, Mohammedia, Morocco.

Quantitative structure-diastereoselectivity relationships were studied for the intermolecular radical addition of deuterium and allyltributyltin to chiral arylsulfoxides by means of multiple linear regression and artificial neural networks (ANN). The values of diastereoselectivity (% syn) of the compounds studied were well correlated with the descriptors encoding the chemical structure. Using the pertinent descriptors revealed by the regression analysis, a square correlation coefficient of 0.9577 ( s=5.3825) for the training set was obtained for the ANN model in a 2-4-1 configuration. The results obtained from this study indicate that the diastereoselectivity of arylsulfoxide derivatives is strongly dependent on the shape of the R and X groups. FIGURE General structure of alpha-sulfinyl radicals
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http://dx.doi.org/10.1007/s00894-003-0136-yDOI Listing
August 2003
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