Piperidinopropiyonafton hidroklorür bileşiğinin tip I ve tip II memeli DNA topoizomeraz enzimleri üzerindeki etkisi

Translated title of the contribution: The interference of piperidinopropionaphthone hydrochloride in mammalian type I and type II DNA topoisomerase reactions

Huseyin Istanbullu, Sevil Zencir, Agnes Berenyi, Pakize Canturk Kilickaya, I. Zupkó, Ercin Erciyas, Zeki Topcu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Majority of anti-cancer drugs were shown to exert their activities by interfering with DNA topoisomerase reactions. Since the identification of Camptothecin as the topoisomerase I targeting compound, these enzymes are widely utilized in biological assays to assess the pharmaceutical significance of the synthetic and natural agents. Because a considerable number of compounds were shown to have cytostatic activities via blocking topoisomerase reactions, we aimed to identify if the previously-reported physiological activities of acetonapthones involves the interference with topoisomerase reactions. We covered topoisomerase activity and cytostatic activity evaluation of piperidinopropionaphthone hydrochloride type Mannich base (MB) to compare its bioactivities to the starting propionaphtone in order to assess the contribution of aminomethyl moiety of the compound on its bioactivity. MB was synthesized and characterized in our laboratory. Supercoiled plasmid relaxation and decatenation assays were carried out to evaluate their biological activities in mammalian DNA topoisomerases. We also assayed the cytostatic activities using HeLa, MCF7 and A431 cell lines. Our data showed a considerable inhibition of MB on type I and type II DNA topoisomerases without a correlation to cytostatic assays. MB exerted a modest activity against the proliferation of MCF7 cells with an IC50 value of 27.62 μM. The presence of MB inhibited topo II decatenation activity as well. Results offer no direct explanation for the contradictory effects on the DNA topoisomerases and the proliferation of cancer cells in vitro. Our results are discussed in relation to potential significance of aminomethyl group of Mannich base in the course of drug-development studies.

Original languageUndefined/Unknown
Pages (from-to)82-87
Number of pages6
JournalMarmara Pharmaceutical Journal
Volume19
Issue number2
DOIs
Publication statusPublished - 2015

Fingerprint

Mannich Bases
Type II DNA Topoisomerase
Type I DNA Topoisomerase
Cytostatic Agents
DNA Topoisomerases
MCF-7 Cells
Pharmaceutical Preparations
Camptothecin
Biological Assay
Inhibitory Concentration 50
Neoplasms
Plasmids
Cell Proliferation
Cell Line
Enzymes

Keywords

  • Anti-cancer drugs
  • Decatenation
  • Mannich base
  • Topoisomerase I
  • Topoisomerase II

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Cite this

Piperidinopropiyonafton hidroklorür bileşiğinin tip I ve tip II memeli DNA topoizomeraz enzimleri üzerindeki etkisi. / Istanbullu, Huseyin; Zencir, Sevil; Berenyi, Agnes; Canturk Kilickaya, Pakize; Zupkó, I.; Erciyas, Ercin; Topcu, Zeki.

In: Marmara Pharmaceutical Journal, Vol. 19, No. 2, 2015, p. 82-87.

Research output: Contribution to journalArticle

Istanbullu, Huseyin ; Zencir, Sevil ; Berenyi, Agnes ; Canturk Kilickaya, Pakize ; Zupkó, I. ; Erciyas, Ercin ; Topcu, Zeki. / Piperidinopropiyonafton hidroklorür bileşiğinin tip I ve tip II memeli DNA topoizomeraz enzimleri üzerindeki etkisi. In: Marmara Pharmaceutical Journal. 2015 ; Vol. 19, No. 2. pp. 82-87.
@article{45a61b730422497683d4f7f9c985983b,
title = "Piperidinopropiyonafton hidroklor{\"u}r bileşiğinin tip I ve tip II memeli DNA topoizomeraz enzimleri {\"u}zerindeki etkisi",
abstract = "Majority of anti-cancer drugs were shown to exert their activities by interfering with DNA topoisomerase reactions. Since the identification of Camptothecin as the topoisomerase I targeting compound, these enzymes are widely utilized in biological assays to assess the pharmaceutical significance of the synthetic and natural agents. Because a considerable number of compounds were shown to have cytostatic activities via blocking topoisomerase reactions, we aimed to identify if the previously-reported physiological activities of acetonapthones involves the interference with topoisomerase reactions. We covered topoisomerase activity and cytostatic activity evaluation of piperidinopropionaphthone hydrochloride type Mannich base (MB) to compare its bioactivities to the starting propionaphtone in order to assess the contribution of aminomethyl moiety of the compound on its bioactivity. MB was synthesized and characterized in our laboratory. Supercoiled plasmid relaxation and decatenation assays were carried out to evaluate their biological activities in mammalian DNA topoisomerases. We also assayed the cytostatic activities using HeLa, MCF7 and A431 cell lines. Our data showed a considerable inhibition of MB on type I and type II DNA topoisomerases without a correlation to cytostatic assays. MB exerted a modest activity against the proliferation of MCF7 cells with an IC50 value of 27.62 μM. The presence of MB inhibited topo II decatenation activity as well. Results offer no direct explanation for the contradictory effects on the DNA topoisomerases and the proliferation of cancer cells in vitro. Our results are discussed in relation to potential significance of aminomethyl group of Mannich base in the course of drug-development studies.",
keywords = "Anti-cancer drugs, Decatenation, Mannich base, Topoisomerase I, Topoisomerase II",
author = "Huseyin Istanbullu and Sevil Zencir and Agnes Berenyi and {Canturk Kilickaya}, Pakize and I. Zupk{\'o} and Ercin Erciyas and Zeki Topcu",
year = "2015",
doi = "10.12991/mpj.2015199638",
language = "Undefined/Unknown",
volume = "19",
pages = "82--87",
journal = "Marmara Pharmaceutical Journal",
issn = "1309-0801",
publisher = "Marmara University",
number = "2",

}

TY - JOUR

T1 - Piperidinopropiyonafton hidroklorür bileşiğinin tip I ve tip II memeli DNA topoizomeraz enzimleri üzerindeki etkisi

AU - Istanbullu, Huseyin

AU - Zencir, Sevil

AU - Berenyi, Agnes

AU - Canturk Kilickaya, Pakize

AU - Zupkó, I.

AU - Erciyas, Ercin

AU - Topcu, Zeki

PY - 2015

Y1 - 2015

N2 - Majority of anti-cancer drugs were shown to exert their activities by interfering with DNA topoisomerase reactions. Since the identification of Camptothecin as the topoisomerase I targeting compound, these enzymes are widely utilized in biological assays to assess the pharmaceutical significance of the synthetic and natural agents. Because a considerable number of compounds were shown to have cytostatic activities via blocking topoisomerase reactions, we aimed to identify if the previously-reported physiological activities of acetonapthones involves the interference with topoisomerase reactions. We covered topoisomerase activity and cytostatic activity evaluation of piperidinopropionaphthone hydrochloride type Mannich base (MB) to compare its bioactivities to the starting propionaphtone in order to assess the contribution of aminomethyl moiety of the compound on its bioactivity. MB was synthesized and characterized in our laboratory. Supercoiled plasmid relaxation and decatenation assays were carried out to evaluate their biological activities in mammalian DNA topoisomerases. We also assayed the cytostatic activities using HeLa, MCF7 and A431 cell lines. Our data showed a considerable inhibition of MB on type I and type II DNA topoisomerases without a correlation to cytostatic assays. MB exerted a modest activity against the proliferation of MCF7 cells with an IC50 value of 27.62 μM. The presence of MB inhibited topo II decatenation activity as well. Results offer no direct explanation for the contradictory effects on the DNA topoisomerases and the proliferation of cancer cells in vitro. Our results are discussed in relation to potential significance of aminomethyl group of Mannich base in the course of drug-development studies.

AB - Majority of anti-cancer drugs were shown to exert their activities by interfering with DNA topoisomerase reactions. Since the identification of Camptothecin as the topoisomerase I targeting compound, these enzymes are widely utilized in biological assays to assess the pharmaceutical significance of the synthetic and natural agents. Because a considerable number of compounds were shown to have cytostatic activities via blocking topoisomerase reactions, we aimed to identify if the previously-reported physiological activities of acetonapthones involves the interference with topoisomerase reactions. We covered topoisomerase activity and cytostatic activity evaluation of piperidinopropionaphthone hydrochloride type Mannich base (MB) to compare its bioactivities to the starting propionaphtone in order to assess the contribution of aminomethyl moiety of the compound on its bioactivity. MB was synthesized and characterized in our laboratory. Supercoiled plasmid relaxation and decatenation assays were carried out to evaluate their biological activities in mammalian DNA topoisomerases. We also assayed the cytostatic activities using HeLa, MCF7 and A431 cell lines. Our data showed a considerable inhibition of MB on type I and type II DNA topoisomerases without a correlation to cytostatic assays. MB exerted a modest activity against the proliferation of MCF7 cells with an IC50 value of 27.62 μM. The presence of MB inhibited topo II decatenation activity as well. Results offer no direct explanation for the contradictory effects on the DNA topoisomerases and the proliferation of cancer cells in vitro. Our results are discussed in relation to potential significance of aminomethyl group of Mannich base in the course of drug-development studies.

KW - Anti-cancer drugs

KW - Decatenation

KW - Mannich base

KW - Topoisomerase I

KW - Topoisomerase II

UR - http://www.scopus.com/inward/record.url?scp=84931053107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84931053107&partnerID=8YFLogxK

U2 - 10.12991/mpj.2015199638

DO - 10.12991/mpj.2015199638

M3 - Article

AN - SCOPUS:84931053107

VL - 19

SP - 82

EP - 87

JO - Marmara Pharmaceutical Journal

JF - Marmara Pharmaceutical Journal

SN - 1309-0801

IS - 2

ER -