Synthesis, Characterisation and Antiviral Activity of Platinum(II) Complexes with 1,10‐Phenanthrolines and the Antiviral Agents Acyclovir and Penciclovir
Identifieur interne : 003506 ( Main/Exploration ); précédent : 003505; suivant : 003507Synthesis, Characterisation and Antiviral Activity of Platinum(II) Complexes with 1,10‐Phenanthrolines and the Antiviral Agents Acyclovir and Penciclovir
Auteurs : Nicola Margiotta [Italie] ; Francesco P. Fanizzi [Italie] ; Joze Kobe [Slovénie] ; Giovanni Natile [Italie]Source :
- European Journal of Inorganic Chemistry [ 1434-1948 ] ; 2001-05.
English descriptors
- Teeft :
- Acyclovir, Antiviral, Antiviral activity, Cd3od, Chem, Chemical shifts, Cisplatin, Coordination plane, Coordination sphere, Dalton trans, Diastereotopic splitting, Diethyl ether, Ether, Fanizzi, Free acyclovir, Full paper, Greater stability, Guanine, Guanine bases, Inorg, Interconversion, Kobe, Ligand, Me2phen, Metal centre, Methanol, Methyl, Methyl substituents, Mmol, Natile, Ortho, Ortho positions, Penciclovir, Phen, Phen ligand, Phenanthroline, Physiological medium, Platinum, Platinum complexes, Purine, Purine base, Room temperature, Rotamers, Slow interconversion, Steric, Steric bulk, Steric interaction, Stoichiometric amount, Substituents, Time scale, Unexpected result.
Abstract
Four novel hybrid drugs [Pt(acy)2(Me2phen)]I2 (1), [Pt(pen)2(Me2phen)](NO3)2 (2), [Pt(acy)2(phen)](NO3)2 (3), and [Pt(pen)2(phen)](NO3)2 (4) have been prepared by reaction of the antiviral guanine derivatives acyclovir (acy) and penciclovir (pen) with platinum complexes having 2,9‐Me2‐1,10‐phenanthroline (Me2phen) and 1,10‐phenanthroline (phen) as carrier ligands. Both the Me2phen and phen carrier ligands are able to hinder rotation of the guanine bases about the Pt−N(7) bonds rendering the interconversion among rotamers very slow on the NMR time scale. A favourable dipole−dipole interaction between the cis‐coordinated purine bases stabilises the HT rotamers, which are the only species detected in solution. The stability in a physiological medium and the anti‐HIV properties in vitro of the complexes have been evaluated. In a 0.1 M solution of NaCl, the compounds with Me2phen (1 and 2) were found to be very stable while the compounds with phen (3 and 4) underwent displacement of one purine base by a chloride ion. This rather unexpected result may have some relevance in connection with the stability of major DNA adducts of cisplatin in which two guanines are cross‐linked by a Pt(NH3)2 moiety. Although none of the complexes showed anti‐HIV activity, complexes 1 and 2, bearing methyl substituents in the ortho positions of the phenanthroline, were much more cytotoxic than 3 and 4. This is probably due to a greater stability of the former complexes in biological media caused by the presence of the two methyl groups wrapping the metal centre and inhibiting the nucleophilic attack of an incoming ligand at the platinum centre.
Url:
DOI: 10.1002/1099-0682(200105)2001:5<1303::AID-EJIC1303>3.0.CO;2-M
Affiliations:
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Fanizzi</name></author><author><name sortKey="Kobe, Joze" sort="Kobe, Joze" uniqKey="Kobe J" first="Joze" last="Kobe">Joze Kobe</name></author><author><name sortKey="Natile, Giovanni" sort="Natile, Giovanni" uniqKey="Natile G" first="Giovanni" last="Natile">Giovanni Natile</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:F5F9CAA3DBD18B25A8E07A1B8965F68E4407C9D1</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1002/1099-0682(200105)2001:5<1303::AID-EJIC1303>3.0.CO;2-M</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-PB3796X4-W/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001413</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001413</idno><idno type="wicri:Area/Istex/Curation">001413</idno><idno type="wicri:Area/Istex/Checkpoint">000E28</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000E28</idno><idno type="wicri:doubleKey">1434-1948:2001:Margiotta N:synthesis:characterisation:and</idno><idno type="wicri:Area/Main/Merge">003544</idno><idno type="wicri:Area/Main/Curation">003506</idno><idno type="wicri:Area/Main/Exploration">003506</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Synthesis, Characterisation and Antiviral Activity of Platinum(II) Complexes with 1,10‐Phenanthrolines and the Antiviral Agents Acyclovir and Penciclovir</title><author><name sortKey="Margiotta, Nicola" sort="Margiotta, Nicola" uniqKey="Margiotta N" first="Nicola" last="Margiotta">Nicola Margiotta</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento Farmaco‐Chimico, Università di Bari, Via E. 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Fanizzi</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento di Biologia, Università di Lecce, Via Monteroni, 73100 Lecce</wicri:regionArea><wicri:noRegion>73100 Lecce</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Consortium CARSO Cancer Research Center, 70100 Valenzano, Bari</wicri:regionArea><wicri:noRegion>Bari</wicri:noRegion></affiliation></author><author><name sortKey="Kobe, Joze" sort="Kobe, Joze" uniqKey="Kobe J" first="Joze" last="Kobe">Joze Kobe</name><affiliation wicri:level="1"><country xml:lang="fr">Slovénie</country><wicri:regionArea>National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana</wicri:regionArea><wicri:noRegion>1000 Ljubljana</wicri:noRegion></affiliation></author><author><name sortKey="Natile, Giovanni" sort="Natile, Giovanni" uniqKey="Natile G" first="Giovanni" last="Natile">Giovanni Natile</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Dipartimento Farmaco‐Chimico, Università di Bari, Via E. Orabona 4, 70125 Bari</wicri:regionArea><wicri:noRegion>70125 Bari</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Italie</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">European Journal of Inorganic Chemistry</title><title level="j" type="alt">EUROPEAN JOURNAL OF INORGANIC CHEMISTRY</title><idno type="ISSN">1434-1948</idno><idno type="eISSN">1099-0682</idno><imprint><biblScope unit="vol">2001</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="1303">1303</biblScope><biblScope unit="page" to="1310">1310</biblScope><biblScope unit="page-count">8</biblScope><publisher>WILEY‐VCH Verlag GmbH</publisher><pubPlace>Weinheim</pubPlace><date type="published" when="2001-05">2001-05</date></imprint><idno type="ISSN">1434-1948</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1434-1948</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acyclovir</term><term>Antiviral</term><term>Antiviral activity</term><term>Cd3od</term><term>Chem</term><term>Chemical shifts</term><term>Cisplatin</term><term>Coordination plane</term><term>Coordination sphere</term><term>Dalton trans</term><term>Diastereotopic splitting</term><term>Diethyl ether</term><term>Ether</term><term>Fanizzi</term><term>Free acyclovir</term><term>Full paper</term><term>Greater stability</term><term>Guanine</term><term>Guanine bases</term><term>Inorg</term><term>Interconversion</term><term>Kobe</term><term>Ligand</term><term>Me2phen</term><term>Metal centre</term><term>Methanol</term><term>Methyl</term><term>Methyl substituents</term><term>Mmol</term><term>Natile</term><term>Ortho</term><term>Ortho positions</term><term>Penciclovir</term><term>Phen</term><term>Phen ligand</term><term>Phenanthroline</term><term>Physiological medium</term><term>Platinum</term><term>Platinum complexes</term><term>Purine</term><term>Purine base</term><term>Room temperature</term><term>Rotamers</term><term>Slow interconversion</term><term>Steric</term><term>Steric bulk</term><term>Steric interaction</term><term>Stoichiometric amount</term><term>Substituents</term><term>Time scale</term><term>Unexpected result</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Four novel hybrid drugs [Pt(acy)2(Me2phen)]I2 (1), [Pt(pen)2(Me2phen)](NO3)2 (2), [Pt(acy)2(phen)](NO3)2 (3), and [Pt(pen)2(phen)](NO3)2 (4) have been prepared by reaction of the antiviral guanine derivatives acyclovir (acy) and penciclovir (pen) with platinum complexes having 2,9‐Me2‐1,10‐phenanthroline (Me2phen) and 1,10‐phenanthroline (phen) as carrier ligands. Both the Me2phen and phen carrier ligands are able to hinder rotation of the guanine bases about the Pt−N(7) bonds rendering the interconversion among rotamers very slow on the NMR time scale. A favourable dipole−dipole interaction between the cis‐coordinated purine bases stabilises the HT rotamers, which are the only species detected in solution. The stability in a physiological medium and the anti‐HIV properties in vitro of the complexes have been evaluated. In a 0.1 M solution of NaCl, the compounds with Me2phen (1 and 2) were found to be very stable while the compounds with phen (3 and 4) underwent displacement of one purine base by a chloride ion. This rather unexpected result may have some relevance in connection with the stability of major DNA adducts of cisplatin in which two guanines are cross‐linked by a Pt(NH3)2 moiety. Although none of the complexes showed anti‐HIV activity, complexes 1 and 2, bearing methyl substituents in the ortho positions of the phenanthroline, were much more cytotoxic than 3 and 4. This is probably due to a greater stability of the former complexes in biological media caused by the presence of the two methyl groups wrapping the metal centre and inhibiting the nucleophilic attack of an incoming ligand at the platinum centre.</div></front></TEI><affiliations><list><country><li>Italie</li><li>Slovénie</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Margiotta, Nicola" sort="Margiotta, Nicola" uniqKey="Margiotta N" first="Nicola" last="Margiotta">Nicola Margiotta</name></noRegion><name sortKey="Fanizzi, Francesco P" sort="Fanizzi, Francesco P" uniqKey="Fanizzi F" first="Francesco P." last="Fanizzi">Francesco P. Fanizzi</name><name sortKey="Fanizzi, Francesco P" sort="Fanizzi, Francesco P" uniqKey="Fanizzi F" first="Francesco P." last="Fanizzi">Francesco P. Fanizzi</name><name sortKey="Natile, Giovanni" sort="Natile, Giovanni" uniqKey="Natile G" first="Giovanni" last="Natile">Giovanni Natile</name><name sortKey="Natile, Giovanni" sort="Natile, Giovanni" uniqKey="Natile G" first="Giovanni" last="Natile">Giovanni Natile</name></country><country name="Slovénie"><noRegion><name sortKey="Kobe, Joze" sort="Kobe, Joze" uniqKey="Kobe J" first="Joze" last="Kobe">Joze Kobe</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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