Synthesis, biological activity, and evaluation of the mode of action of novel antitubercular benzofurobenzopyrans substituted on A ring
| Autor: | Yves L. Janin, Jana Korduláková, Mary Jackson, Roland Brosch, François Tillequin, Fabienne Bardou, Inana Khouri, Soizic Prado, Brigitte Saint-Joanis, Sylvie Michel, Ioannis S. Vizirianakis, Elsa P. Amanatiadou, Aikaterini Termentzi, Mamadou Daffé, Thomas Gaslonde |
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| Přispěvatelé: | Synthèse et structure de molécules d'interet pharmacologique (SSMIP), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Molécules de Communication et Adaptation des Micro-Organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire Bactérienne, Institut Pasteur [Paris], Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratory of Pharmacology, Aristotle University of Thessaloniki, Faculty of Natural Sciences, Comenius University in Bratislava, Mycobacteria Research Laboratories, Colorado State University [Fort Collins] (CSU), Chimie Organique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Synthèse et structure de molécules d'interet pharmacologique ( SSMIP ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Molécules de Communication et Adaptation des Micro-Organismes ( MCAM ), Muséum National d'Histoire Naturelle ( MNHN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de pharmacologie et de biologie structurale ( IPBS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Comenius University, Colorado State University [Fort Collins] ( CSU ), Chimie Organique ( UCO ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Comenius University [Bratislava], Chimie Organique (UCO) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Stereochemistry
medicine.drug_class Antitubercular Agents Microbial Sensitivity Tests 010402 general chemistry Ring (chemistry) Antimycobacterial 01 natural sciences Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Nucleophilic aromatic substitution Chlorocebus aethiops Drug Discovery medicine Animals Structure–activity relationship Benzopyrans Vero Cells Benzofurans Antibacterial agent Pharmacology Cell Death Molecular Structure 010405 organic chemistry Organic Chemistry Stereoisomerism Mycobacterium tuberculosis General Medicine Mycobacterium bovis 0104 chemical sciences 3. Good health Benzopyran chemistry Pyran |
| Zdroj: | European Journal of Medicinal Chemistry European Journal of Medicinal Chemistry, Elsevier, 2010, 45 (12), pp.5833-47. ⟨10.1016/j.ejmech.2010.09.048⟩ European Journal of Medicinal Chemistry, 2010, 45 (12), pp.5833-47. ⟨10.1016/j.ejmech.2010.09.048⟩ European Journal of Medicinal Chemistry, Elsevier, 2010, 45 (12), pp.5833-47. 〈10.1016/j.ejmech.2010.09.048〉 |
| ISSN: | 0223-5234 1768-3254 |
| DOI: | 10.1016/j.ejmech.2010.09.048⟩ |
| Popis: | International audience; The 8-, 9-, 10-, and 11-halo, hydroxy, and methoxy derivatives of the antimycobacterial 3,3-dimethyl-3H-benzofuro[3,2-f][1]benzopyran were synthesized by condensation of the diazonium salts of 2-chloroanilines (13-17) with 1,4-benzoquinone (18), reduction of the intermediate phenylbenzoquinones 19-22 to dihydroxybiphenyls, cyclisation to halo-2-hydroxydibenzofurans 24-27, and construction of the pyran ring by thermal rearrangement of the corresponding dimethylpropargyl ethers 35-38. Palladium catalyzed nucleophilic aromatic substitution permitted conversion of the halo to the corresponding hydroxy derivatives which were methylated to methoxy-3,3-dimethyl-3H-benzofuro[3,2-f][1]benzopyran. All compounds substituted on the A ring were found more potent than the reference compound 1 against Mycobacterium bovis BCG and the virulent strain Mycobacterium tuberculosis H37Rv. The effect of the most active derivatives on mycolate synthesis was explored in order to confirm the preliminary hypothesis of an effect on mycobacterial cell wall biosynthesis. The linear 9-methoxy-2,2-dimethyl-2H-benzofuro[2,3-g][1]benzopyran (46) exhibiting a good antimycobacterial activity and devoid of cytotoxicity appeared to be the most promising compound. |
| Databáze: | OpenAIRE |
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