The hybrid models, containing hydrolytic and electron-driven processes, in theoretical study of oxaliplatin biotransform
- PDF / 2,413,972 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 64 Downloads / 137 Views
ORIGINAL PAPER
The hybrid models, containing hydrolytic and electron-driven processes, in theoretical study of oxaliplatin biotransformation Janina Kuduk-Jaworska 1 & Jerzy J. Jański 1 & Szczepan Roszak 2 Received: 9 July 2020 / Accepted: 15 September 2020 / Published online: 26 September 2020 # The Author(s) 2020
Abstract The results of theoretical simulations of reaction paths for oxaliplatin from pro-drug into its active form responsible for cytostatic effect are presented. The studies based on the quantum-chemical density functional theory approach were performed considering environmental influence resulting from the aquation or electron donation. The hybrid mechanisms: hydrolytic mixed with electron driven were found to be the energetically favourable. Keywords Oxaliplatin transformation . Electron-driven reactions . DFT calculations . Hybrid mechanism . Nonclassical Pt-water interactions
Introduction The costly and time-consuming studies, including chemical, physical, biological and pharmacological procedures, are necessary to establish if the evaluated compound can be introduced into the market as an approved drug. Statistically, only one in 5000 to 10,000 compounds directed to in vitro tests becomes officially recognized drug [1]. The search for anticancer drugs proved more efficient in metal compounds, but the results are not satisfying either. So far, over 3000 platinum coordination compounds have been evaluated in vitro, out of which three compounds were selected and registered worldwide for use in the standard treatment of cancer [2]. This paper belongs to the Topical Collection Zdzislaw Latajka 70th Birthday Festschrift This paper is in honour of professor Zdzisƚaw Latajka on his 45 years of research. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00894-020-04549-4) contains supplementary material, which is available to authorized users. * Szczepan Roszak [email protected] 1
Faculty of Chemistry, Wrocław University, F. Joliot-Curie 14, 50-370 Wrocław, Poland
2
Department of Physical and Quantum Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland
Oxaliplatin (IUPAC Name: (1R,2R)-cyclohexane-1,2diamine;oxalate;platinum(2+)) constitutes a platinum-based drug of the latest generation. This medicine, as Eloxatin™ for injection in combination with infusional 5-fluorouracil and leucovorin, was approved by FDA in 2002 for the treatment of patients with metastatic carcinoma of the colon or rectum. It was introduced by the USA in 2002, but earlier was registered for the treatment of advanced colorectal cancer (ACRC) in France (1996) and by European Union (1999) [3, 4]. Oxaliplatin (Fig. 1), similarly as two earlier available drugs, cisplatin and carboplatin, belongs to the family of neutral platinum(II) complexes, characterized by the square motive at the Pt center. The important advantage of oxaliplatin is the lack of tumour cross-resistance with cisplatin and carboplatin, whi
Data Loading...
