NDLI: Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes

Please wait, while we are loading the content...

New tungstenocenes containing 3-hydroxy-4-pyrone ligands: antiproliferative activity on HT-29 and MCF-7 cell lines and binding to human serum albumin studied by fluorescence spectroscopy and molecular modeling methods

Coordination of peroxide to the CuM center of peptidylglycine α-hydroxylating monooxygenase (PHM): structural and computational study

Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes

Year: 2013, Volume: 18, Issue: 1

Year: 2012, Volume: 17

Year: 2011, Volume: 16

Year: 2010, Volume: 15

Year: 2009, Volume: 14 Suppl 1

Year: 2009, Volume: 14

Year: 2008, Volume: 13

Year: 2007, Volume: 12

Year: 2004, Volume: 9

Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes

Content Provider	PubMed Central
Author	Valiahdi, Seied Mojtaba Egger, Alexander E. Miklos, Walter Jungwirth, Ute Kristof, Meelich Nock, Petra Berger, Walter Hartinger, Christian G. Markus, Galanski Jakupec, Michael A. Keppler, Bernhard K.
Copyright Year	2013
Abstract	Extracellular acidity is a frequent pathophysiological condition of solid tumors offering possibilities for improving the tumor selectivity of molecular therapy. This might be accomplished by prodrugs with low systemic toxicity, attaining their full antitumor potency only under acidic conditions, such as bis(2-aminoalcoholato-κ2 N,O)platinum(II) complexes that are activated by protonation of alcoholato oxygen, resulting in cleavage of platinum–oxygen bonds. In this work, we examined whether the pH dependency of such compounds is reflected in differential biological activity in vitro. In particular, the pH dependence of cytotoxicity, cellular accumulation, DNA platination, GMP binding, effects on DNA secondary structure, cell cycle alterations, and induction of apoptosis was investigated. Enhanced cytotoxicity of five of these complexes in non-small-cell lung cancer (A549) and colon carcinoma (HT-29) cells at pH 6.0 in comparison with pH 7.4 was confirmed: 50 % growth inhibition concentrations ranged from 42 to 214 μM in A549 cells and from 35 to 87 μM in HT-29 cells at pH 7.4 and decreased at pH 6.0 to 11–50 and 7.3–25 μM, respectively. The effects induced by all five pH-sensitive compounds involve increased 5′-GMP binding, cellular accumulation, and DNA platination as well as stronger effects on DNA secondary structure at pH 6.0 than at pH 7.4. As exemplified by treatment of A549 cells with a 2-amino-4-methyl-1-pentanolato complex, induction of apoptosis is enhanced at pH 6.5. These results confirm the increased reactivity and in vitro activity of these compounds under slightly acidic conditions, encouraging further evaluation of ring-closed aminoalcoholatoplatinum(II) derivatives in solid tumors in vivo.
Related Links	http://dx.doi.org/10.1007/s00775-012-0970-4
Ending Page	260
Page Count	12
Starting Page	249
File Format	PDF
ISSN	14321327
e-ISSN	14321327
Journal	Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
Issue Number	2
Volume Number	18
Language	English
Publisher Date	2013-02-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biochemistry Inorganic Chemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes

Synthesis, characterization, and DNA binding, photocleavage, cytotoxicity, cellular uptake, apoptosis, and on–off light switching studies of Ru(II) mixed-ligand complexes containing 7-fluorodipyrido[3,2-a:2′,3′-c]phenazine

Novel palladium(II) complexes containing a sulfur ligand: structure and biological activity on HeLa cells

Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines

Synthesis, Characterization and Cytotoxicity Studies of Palladium(II)-Proflavine Complexes

Cellular accumulation and DNA interaction studies of cytotoxic trans-platinum anticancer compounds

Structure–activity relationship study of copper(II) complexes with 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (4′-methylbenzoyl) hydrazone: synthesis, structures, DNA and protein interaction studies, antioxidative and cytotoxic activity

Two New Mononuclear Copper(II)-Dipeptide Complexes of 2-(2′-Pyridyl)Benzoxazole: DNA Interaction, Antioxidation and in Vitro Cytotoxicity Studies

Exploring the Cellular Accumulation of Metal Complexes

Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes

Similar Documents

Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes

Synthesis, characterization, and DNA binding, photocleavage, cytotoxicity, cellular uptake, apoptosis, and on–off light switching studies of Ru(II) mixed-ligand complexes containing 7-fluorodipyrido[3,2-a:2′,3′-c]phenazine

Novel palladium(II) complexes containing a sulfur ligand: structure and biological activity on HeLa cells

Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines

Synthesis, Characterization and Cytotoxicity Studies of Palladium(II)-Proflavine Complexes

Cellular accumulation and DNA interaction studies of cytotoxic trans-platinum anticancer compounds

Structure–activity relationship study of copper(II) complexes with 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (4′-methylbenzoyl) hydrazone: synthesis, structures, DNA and protein interaction studies, antioxidative and cytotoxic activity

Two New Mononuclear Copper(II)-Dipeptide Complexes of 2-(2′-Pyridyl)Benzoxazole: DNA Interaction, Antioxidation and in Vitro Cytotoxicity Studies

Exploring the Cellular Accumulation of Metal Complexes

Influence of extracellular pH on the cytotoxicity, cellular accumulation, and DNA interaction of novel pH-sensitive 2-aminoalcoholatoplatinum(II) complexes