In Vitro Anticancer Activities and Optical Imaging of Novel Intercalative Non-Cisplatin Conjugates
Identifieur interne : 001E18 ( Main/Exploration ); précédent : 001E17; suivant : 001E19In Vitro Anticancer Activities and Optical Imaging of Novel Intercalative Non-Cisplatin Conjugates
Auteurs : Jian Gao [États-Unis] ; F. Ross Woolley [États-Unis] ; Ralph A. Zingaro [États-Unis]Source :
- Journal of Medicinal Chemistry [ 0022-2623 ] ; 2005.
Abstract
The first π-conjugated macrocyclic diimine and triaza DNA-binding intercalators and their platinum(II) conjugates have been synthesized by direct Schiff base cyclocondensation. The in vitro anticancer activities of compounds 3, 4, and 5 were tested on five cancer cell lines: MCF-7, A549, P388, A2780, and A2780cisR. Ovarian tumors were included specifically to evaluate the new conjugates' ability to circumvent A2780cisR resistance. Antitumor effects of the newly conjugated compounds were compared to those of cisplatin. The data clearly indicate that improved drug efficiencies are achieved as a result of the intercalative moieties. The luminescent probe that was integrated in complexes 8−10 made it possible to monitor drug penetration using optical imaging. Enhanced targeting of tumor nuclei by the study compounds was confirmed by confocal microscopy. This paper describes a new class of platinum-based antitumorals differing from cisplatin in several critical aspects with the potential for significantly improving clinical outcomes in cancer patients.
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DOI: 10.1021/jm050497t
Affiliations:
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Non-Cisplatin Conjugates</title><author><name sortKey="Gao, Jian" sort="Gao, Jian" uniqKey="Gao J" first="Jian" last="Gao">Jian Gao</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Radiology, School of Medicine, University of Texas Health Science Center at San Antonio, Texas 78229-3900,and Department of Chemistry, Texas A & M University, College Station</wicri:cityArea></affiliation><affiliation></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author><author><name sortKey="Woolley, F Ross" sort="Woolley, F Ross" uniqKey="Woolley F" first="F. Ross" last="Woolley">F. Ross Woolley</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Radiology, School of Medicine, University of Texas Health Science Center at San Antonio, Texas 78229-3900,and Department of Chemistry, Texas A & M University, College Station</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Zingaro, Ralph A" sort="Zingaro, Ralph A" uniqKey="Zingaro R" first="Ralph A." last="Zingaro">Ralph A. Zingaro</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Department of Radiology, School of Medicine, University of Texas Health Science Center at San Antonio, Texas 78229-3900,and Department of Chemistry, Texas A & M University, College Station</wicri:cityArea></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Medicinal Chemistry</title><title level="j" type="abbrev">J. Med. Chem.</title><idno type="ISSN">0022-2623</idno><idno type="eISSN">1520-4804</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="2005-10-25">2005</date><date when="2005-11-17">2005</date><biblScope unit="vol">48</biblScope><biblScope unit="issue">23</biblScope><biblScope unit="page" from="7192">7192</biblScope><biblScope unit="page" to="7197">7197</biblScope></imprint><idno type="ISSN">0022-2623</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2623</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">The first π-conjugated macrocyclic diimine and triaza DNA-binding intercalators and their platinum(II) conjugates have been synthesized by direct Schiff base cyclocondensation. The in vitro anticancer activities of compounds 3, 4, and 5 were tested on five cancer cell lines: MCF-7, A549, P388, A2780, and A2780cisR. Ovarian tumors were included specifically to evaluate the new conjugates' ability to circumvent A2780cisR resistance. Antitumor effects of the newly conjugated compounds were compared to those of cisplatin. The data clearly indicate that improved drug efficiencies are achieved as a result of the intercalative moieties. The luminescent probe that was integrated in complexes 8−10 made it possible to monitor drug penetration using optical imaging. Enhanced targeting of tumor nuclei by the study compounds was confirmed by confocal microscopy. This paper describes a new class of platinum-based antitumorals differing from cisplatin in several critical aspects with the potential for significantly improving clinical outcomes in cancer patients.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Gao, Jian" sort="Gao, Jian" uniqKey="Gao J" first="Jian" last="Gao">Jian Gao</name></region><name sortKey="Gao, Jian" sort="Gao, Jian" uniqKey="Gao J" first="Jian" last="Gao">Jian Gao</name><name sortKey="Woolley, F Ross" sort="Woolley, F Ross" uniqKey="Woolley F" first="F. Ross" last="Woolley">F. Ross Woolley</name><name sortKey="Zingaro, Ralph A" sort="Zingaro, Ralph A" uniqKey="Zingaro R" first="Ralph A." last="Zingaro">Ralph A. Zingaro</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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