Τόμος 13 (1995) – Τεύχος 4 – Άρθρο 1 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 13 (1995) – Issue 4 – Article 1 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Από | | Άρθρο - Article, Βασίλειος Αλετράς,Vasilis Aletras, Διονύσιος Χατζηλιάδης,Denis Hadjiliadis, Νικόλαος Χατζηλιάδης,Nick Hadjiliadis, Πλήρες Κείμενο στα Ελληνικά - Full Text in Greek

 

Τίτλος – Title

Στοι­χεί­α του Μη­χα­νι­σμού Δρά­σε­ως του Α­ντι­καρ­κι­νι­κού Φαρ­μά­κου cis-Platin (cis-DDP) και των Πα­ρα­γώ­γων του της Δεύτερης Γενεάς

Elements of the Mechanism of Action of the Antitumor Drug cis-Platin or cis-DDP and its Second Generation Derivatives
Συγγραφέας – Author

Βασίλειος Αλετράς1, Διονύσιος Χατζηλιάδης2 και Νικόλαος Χατζηλιάδης1

1 Ερ­γα­στή­ριο Α­νορ­γά­νου και Γε­νι­κής Χη­μεί­ας, Τμή­μα Χη­μεί­ας, Πα­νε­πι­στή­μιο Ιω­αν­νί­νων, Ιω­άν­νι­να 45 110, Ελ­λά­δα 2 Mayo Clinic, Rochester, Minesota, Η­ΠΑ

Vasilis Aletras1, Denis Hadjiliadis1 and Nick Hadjiliadis2

1 Laboratory of Inorganic and General Chemistry, Department of Chemistry, University of Ioannina, GR-451 10 Ioannina, Greece 2 Mayo Clinic, Rochester, Minesota, USA
Παραπομπή – Citation

Αλετράς,Β.,  Χατζηλιάδης, Δ.,  Χατζηλιάδης,Ν. : Στοι­χεί­α του Μη­χα­νι­σμού Δρά­σε­ως του Α­ντι­καρ­κι­νι­κού Φαρ­μά­κου cis-Platin (cis-DDP) και των Πα­ρα­γώ­γων του της Δεύτερης Γενεάς , Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 14 : 153-180 (1996)

Aletras,V.,  Hadjiliadis,D., Hadjiliadis,N. : Elements of the Mechanism of Action of the Antitumor Drug cis-Platin or cis-DDP and its Second Generation Derivatives, Epitheorese Klin. Farmakol. Farmakokinet. 14 : 153-180 (1996)
Ημερομηνία Δημοσιευσης – Publication Date
15-05-1995
Γλώσσα Πλήρους Κειμένου –
Full Text Language

Ελληνικά – Greek
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Λέξεις κλειδιά – Keywords

cis-platin, carboplatin, α­ντι­καρ­κι­νι­κό φάρ­μα­κο, εν­δο­κλω­νι­κός δια­σταυ­ρού­με­νος δε­σμός, δια­κλω­νι­κός διασταυ­ρού­με­νος δε­σμός

cis-platin, carboplatin, anticancer drug, intrastrand crosslink, interstrand crosslink
Λοιποί Όροι – Other Terms

Άρθρο

Article
Περίληψη – Summary

Στο άρ­θρο αυ­τό α­να­σκο­πή­σε­ως α­να­φέ­ρο­νται στοι­χεί­α του μη­χα­νι­σμού δρά­σε­ως του α­ντι­καρ­κι­νι­κού φαρ­μά­κου cis-δια­μι­νο-δι­χλω­ρο-λευ­κό­χρυσος (Ι­Ι) (cis-DDP ή cis-Platin) και των πα­ρα­γώ­γων του δεύ­τε­ρης γεν­εάς. Eéäéêüôåñá, αρχικώς γί­νε­ται ι­στο­ρι­κή α­να­δρο­μή της α­να­κά­λυ­ψης του φαρ­μάκου, της σχέ­σης δο­μής-δρα­στι­κό­τη­τας, των θέ­σε­ων σύν­δε­σής του με τις βά­σεις του DNA και του μη­χα­νι­σμού υ­δρό­λυ­σής του, όπως και του α­νε­νερ­γού trans-DDP σε υ­δα­τι­κά δια­λύ­μα­τα. Α­κο­λου­θεί βι­βλιο­γρα­φι­κή α­να­σκό­πη­ση του τρό­που σύν­δε­σης με­ταλ­λο­ϊ­ό­ντων με το DNA, μέ­σω σχη­μα­τι­σμού συ­μπλό­κου DNA-πα­ρεμ­βο­λέ­ως, συ­μπλό­κου ε­ξω­τε­ρι­κής σφαί­ρας (ιο­νι­κή σύν­δε­ση) και συ­μπλό­κου ε­σω­τε­ρι­κής σφαί­ρας (ομοι­ο­πο­λι­κή σύν­δε­ση). Στη συ­νέ­χει­α α­να­φέ­ρο­νται οι τρό­ποι σύν­δεσε­ως cis- και trans-DDP με DNA και/ή πρω­τεΐνες, μέ­σω εν­δο­κλω­νι­κών 1,2- και 1,3-δια­σταυ­ρού­με­νων δε­σμών, δια­κλω­νι­κών δια­σταυ­ρού­με­νων δε­σμών, δι­δο­ντι­κής σύν­δε­σης του cis-DDP με την ί­δια βά­ση του DNA και δια­σταυ­ρού­με­νων δε­σμών DNA-πρω­τε­ϊ­νών. Πα­ρέ­χο­νται, τέ­λος, στοι­χεί­α φαρ­μα­κο­κι­νη­τι­κής των cis-DDP, paraplatin και iproplatin και ε­ξά­γο­νται τε­λι­κά συ­μπε­ρά­σμα­τα.

The present article attempts to sum­marise the elements of the mechanism of action of the antitumor drug cis-Platin presented the last few years. Highlights on the history of the discov­ery of the drug, the structure-activity relation­ships, the development of its second generation derivatives, the mechanism of hydrolysis of the drug as well as of the inactive congener trans-platin and of its second generation drug carboplat­in, in aqueous solutions, are presented. The way of binding of the metal ions, in general, to the DNA molecule are described, namely intercalation of a complex to the DNA double helix, the forma­tion of outer sphere complex (ionic binding) and the inner sphere complex formation (covalent binding). More extensively are discussed the binding ways (inter- and intra-strand crosslinking, bidentate binding to one DNA base and DNA-Pro­tein crosslinking) and binding sites of cis-Platin and its trans-isomer to biomolecules, such as DNA bases (mainly guanine) and proteins, as well as reactions with their models e.g. nucleotides and nucleosides. Elements of pharmacokinetics for the drug, its trans-isoner and its second gen­eration most successful drug carboplatin are pre­sented. Finally, useful conclusions are given from this work, pointing out the unanswered questions about the action of cis-DDP as well as its differ­ences in action, in comparison with trans-DDP.
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