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Şenel P, Agar S, İş YS, et al. Deciphering the mechanism and binding interactions of Pemetrexed with dsDNA with DNA-targeted chemotherapeutics via spectroscopic, analytical, and simulation studies. J Pharm Biomed Anal. 2021;209:114490doi: 10.1016/j.jpba.2021.114490.
Şenel, P., Agar, S., İş, Y. S., Altay, F., Gölcü, A., & Yurtsever, M. (2022). Deciphering the mechanism and binding interactions of Pemetrexed with dsDNA with DNA-targeted chemotherapeutics via spectroscopic, analytical, and simulation studies. Journal of pharmaceutical and biomedical analysis, 209114490. https://doi.org/10.1016/j.jpba.2021.114490
Şenel, Pelin, et al. "Deciphering the mechanism and binding interactions of Pemetrexed with dsDNA with DNA-targeted chemotherapeutics via spectroscopic, analytical, and simulation studies." Journal of pharmaceutical and biomedical analysis vol. 209 (2022): 114490. doi: https://doi.org/10.1016/j.jpba.2021.114490
Şenel P, Agar S, İş YS, Altay F, Gölcü A, Yurtsever M. Deciphering the mechanism and binding interactions of Pemetrexed with dsDNA with DNA-targeted chemotherapeutics via spectroscopic, analytical, and simulation studies. J Pharm Biomed Anal. 2022 Feb 05;209:114490. doi: 10.1016/j.jpba.2021.114490. Epub 2021 Nov 24. PMID: 34875572.
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J Pharm Biomed Anal. 2022 Feb 05;209:114490. doi: 10.1016/j.jpba.2021.114490. Epub 2021 Nov 24.

Deciphering the mechanism and binding interactions of Pemetrexed with dsDNA with DNA-targeted chemotherapeutics via spectroscopic, analytical, and simulation studies.

Journal of pharmaceutical and biomedical analysis

Pelin Şenel, Soykan Agar, Yusuf Serhat İş, Filiz Altay, Ayşegül Gölcü, Mine Yurtsever

Affiliations

  1. Department of Chemistry, Faculty of Arts and Sciences, Istanbul Technical University, Maslak, Istanbul 34469, Turkey.
  2. Department of Chemical Technology, Istanbul Gedik University, 34876 Istanbul, Turkey.
  3. Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, Istanbul 34469, Turkey.
  4. Department of Chemistry, Faculty of Arts and Sciences, Istanbul Technical University, Maslak, Istanbul 34469, Turkey. Electronic address: [email protected].
  5. Department of Chemistry, Faculty of Arts and Sciences, Istanbul Technical University, Maslak, Istanbul 34469, Turkey. Electronic address: [email protected].

PMID: 34875572 DOI: 10.1016/j.jpba.2021.114490

Abstract

Pemetrexed is a well-known and widely used antineoplastic drug under the category of cytotoxic, folate anti-metabolites that is used in chemotherapeutic treatments, especially in malignant mesothelioma and non-small cell lung carcinoma. Here, the binding mechanism and interactions of Pemetrexed with double strain fish sperm deoxyribonucleic acid (dsDNA) were studied thoroughly both experimentally and theoretically, using multi-spectroscopic techniques and molecular docking simulations. Our ultimate goal is to understand better the potential of such antineoplastic drugs and, hence, to design drugs with high dsDNA binding affinities and fewer adverse effects. We employed several techniques yielding different but complementary results such as UV, fluorescence, thermal denaturation, electrochemical and viscosity, and molecular docking studies under physiological conditions. Our results revealed that the Pemetrexed binds fairly strongly to dsDNA's minor groove through hydrogen bond interactions with the mostly adenine and guanine bases via its p-carbamide and p-carboxylic groups. MD simulations of the drug-dsDNA complex were followed for 50 ns to confirm that interaction is stable and robust electrostatic interactions were due to hydrogen bonding mostly with the adenine and guanine nucleotides in the minor groove.

Copyright © 2021. Published by Elsevier B.V.

Keywords: Antineoplastic drugs; Molecular docking; Pemetrexed; Spectroscopy; dsDNA

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

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