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Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP

Authorized Users Only
2019
Authors
Stanković, Dalibor
Ristić, Slavica M.
Vukadinović, Aleksandar
Mirković, Marija D.
Vladimirov, Sandra S.
Milanović, Zorana
Radović, Magdalena
Mijović, Milica
Stanković, Dalibor
Sabo, Tibor
Vranješ-Đurić, Sanja
Janković, Drina
Article (Published version)
Metadata
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Abstract
It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD 50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day ...dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.

Keywords:
biochemical analysis / DE-EDCP / DNA interaction / hematological parameters / mice / toxicity study
Source:
Human and Experimental Toxicology, 2019, 38, 4, 466-481
Publisher:
  • SAGE PUBLICATIONS LTD
Funding / projects:
  • Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-172035)
  • Magnetic and radionuclide labeled nanostructured materials for medical applications (RS-45015)

DOI: 10.1177/0960327118819047

ISSN: 0960-3271

WoS: 000462049400009

Scopus: 2-s2.0-85060129792
[ Google Scholar ]
URI
https://cherry.chem.bg.ac.rs/handle/123456789/2894
Collections
  • Publikacije
Institution/Community
Hemijski fakultet
TY  - JOUR
AU  - Stanković, Dalibor
AU  - Ristić, Slavica M.
AU  - Vukadinović, Aleksandar
AU  - Mirković, Marija D.
AU  - Vladimirov, Sandra S.
AU  - Milanović, Zorana
AU  - Radović, Magdalena
AU  - Mijović, Milica
AU  - Stanković, Dalibor
AU  - Sabo, Tibor
AU  - Vranješ-Đurić, Sanja
AU  - Janković, Drina
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2894
AB  - It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD 50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.
PB  - SAGE PUBLICATIONS LTD
T2  - Human and Experimental Toxicology
T1  - Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP
VL  - 38
IS  - 4
SP  - 466
EP  - 481
DO  - 10.1177/0960327118819047
ER  - 
@article{
author = "Stanković, Dalibor and Ristić, Slavica M. and Vukadinović, Aleksandar and Mirković, Marija D. and Vladimirov, Sandra S. and Milanović, Zorana and Radović, Magdalena and Mijović, Milica and Stanković, Dalibor and Sabo, Tibor and Vranješ-Đurić, Sanja and Janković, Drina",
year = "2019",
abstract = "It was reported that novel O,O′-diethyl-(S, S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD 50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.",
publisher = "SAGE PUBLICATIONS LTD",
journal = "Human and Experimental Toxicology",
title = "Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP",
volume = "38",
number = "4",
pages = "466-481",
doi = "10.1177/0960327118819047"
}
Stanković, D., Ristić, S. M., Vukadinović, A., Mirković, M. D., Vladimirov, S. S., Milanović, Z., Radović, M., Mijović, M., Stanković, D., Sabo, T., Vranješ-Đurić, S.,& Janković, D.. (2019). Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP. in Human and Experimental Toxicology
SAGE PUBLICATIONS LTD., 38(4), 466-481.
https://doi.org/10.1177/0960327118819047
Stanković D, Ristić SM, Vukadinović A, Mirković MD, Vladimirov SS, Milanović Z, Radović M, Mijović M, Stanković D, Sabo T, Vranješ-Đurić S, Janković D. Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP. in Human and Experimental Toxicology. 2019;38(4):466-481.
doi:10.1177/0960327118819047 .
Stanković, Dalibor, Ristić, Slavica M., Vukadinović, Aleksandar, Mirković, Marija D., Vladimirov, Sandra S., Milanović, Zorana, Radović, Magdalena, Mijović, Milica, Stanković, Dalibor, Sabo, Tibor, Vranješ-Đurić, Sanja, Janković, Drina, "Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP" in Human and Experimental Toxicology, 38, no. 4 (2019):466-481,
https://doi.org/10.1177/0960327118819047 . .

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