DNA cleavage mechanism by metal complexes of Cu(II), Zn(II) and VO(IV) with a schiff-base ligand
Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved..
Metal ions and metal complexes are important components of nucleic acid biochemistry, participating both in regulation of gene expression and as therapeutic agents. Three new transition metal complexes of copper(II), zinc(II) and oxidovanadium(IV) with a ligand derived from o-vanillin and thiophene were previously synthesized and their antitumor properties were studied in our laboratory. To elucidate some molecular mechanisms tending to explain the cytotoxic effects observed over tumor cells, we investigated the interaction of these complexes with DNA by gel electrophoresis, UV-Vis spectroscopy, docking studies and molecular dynamics simulations. Our spectroscopy and computational results have shown that all of them were able to bind to DNA, Cu(II) complex is located in the minor groove while Zn(II) and oxidovanadium(IV) complexes act as major groove binding molecules. Interestingly, only the Cu(II) complex caused double-strand DNA nicks, consistent with its higher cytotoxic activities previously observed in tumor cell lines. We propose that the DNA-complex interaction destabilize the molecule either disrupting the phosphodiester bonds or impairing DNA replication, giving those complexes strong antitumor potential.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:186 |
|---|---|
| Enthalten in: |
Biochimie - 186(2021) vom: 10. Juli, Seite 43-50 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rodríguez, María R [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
3WHH0066W5 |
|---|
| Anmerkungen: |
Date Completed 05.08.2021 Date Revised 05.08.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.biochi.2021.04.002 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM324205767 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM324205767 | ||
| 003 | DE-627 | ||
| 005 | 20231225185824.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.biochi.2021.04.002 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1080.xml |
| 035 | |a (DE-627)NLM324205767 | ||
| 035 | |a (NLM)33865903 | ||
| 035 | |a (PII)S0300-9084(21)00099-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Rodríguez, María R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a DNA cleavage mechanism by metal complexes of Cu(II), Zn(II) and VO(IV) with a schiff-base ligand |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.08.2021 | ||
| 500 | |a Date Revised 05.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved. | ||
| 520 | |a Metal ions and metal complexes are important components of nucleic acid biochemistry, participating both in regulation of gene expression and as therapeutic agents. Three new transition metal complexes of copper(II), zinc(II) and oxidovanadium(IV) with a ligand derived from o-vanillin and thiophene were previously synthesized and their antitumor properties were studied in our laboratory. To elucidate some molecular mechanisms tending to explain the cytotoxic effects observed over tumor cells, we investigated the interaction of these complexes with DNA by gel electrophoresis, UV-Vis spectroscopy, docking studies and molecular dynamics simulations. Our spectroscopy and computational results have shown that all of them were able to bind to DNA, Cu(II) complex is located in the minor groove while Zn(II) and oxidovanadium(IV) complexes act as major groove binding molecules. Interestingly, only the Cu(II) complex caused double-strand DNA nicks, consistent with its higher cytotoxic activities previously observed in tumor cell lines. We propose that the DNA-complex interaction destabilize the molecule either disrupting the phosphodiester bonds or impairing DNA replication, giving those complexes strong antitumor potential | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DNA binding Studies | |
| 650 | 4 | |a Gel electrophoresis | |
| 650 | 4 | |a Schiff bases | |
| 650 | 4 | |a Transition metal complexes | |
| 650 | 7 | |a Schiff Bases |2 NLM | |
| 650 | 7 | |a Vanadates |2 NLM | |
| 650 | 7 | |a 3WHH0066W5 |2 NLM | |
| 650 | 7 | |a Copper |2 NLM | |
| 650 | 7 | |a 789U1901C5 |2 NLM | |
| 650 | 7 | |a DNA |2 NLM | |
| 650 | 7 | |a 9007-49-2 |2 NLM | |
| 650 | 7 | |a Zinc |2 NLM | |
| 650 | 7 | |a J41CSQ7QDS |2 NLM | |
| 700 | 1 | |a Lavecchia, Martín J |e verfasserin |4 aut | |
| 700 | 1 | |a Parajón-Costa, Beatriz S |e verfasserin |4 aut | |
| 700 | 1 | |a González-Baró, Ana C |e verfasserin |4 aut | |
| 700 | 1 | |a González-Baró, María R |e verfasserin |4 aut | |
| 700 | 1 | |a Cattáneo, Elizabeth R |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochimie |d 1971 |g 186(2021) vom: 10. Juli, Seite 43-50 |w (DE-627)NLM000014419 |x 1638-6183 |7 nnns |
| 773 | 1 | 8 | |g volume:186 |g year:2021 |g day:10 |g month:07 |g pages:43-50 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.biochi.2021.04.002 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 186 |j 2021 |b 10 |c 07 |h 43-50 | ||