Synthesis and structural characterisation of novel platinum-based drug candidates with extended functionality by incorporation of bis(diphenylphosphino)ferrocene units as metal chelators
(2006) In Tetrahedron 62(18). p.4519-4527- Abstract
- Among the metal-based anticancer drugs, cisplatin (cis-diaminedichloroplatinum(II)) is the most widely used species in therapy. Despite its clinical success, cisplatin still suffers in generating resistance, as well as being highly toxic due to poor selectivity between healthy and sick cells. By molecular design it ought to be possible to generate new cis-platinum compounds with increased selectivity and improved cellular behaviour. In this paper, we report a synthetic pathway for construction of derivatives of 1,1'-bis(diphenylphosphino)-ferrocene, together with their corresponding cis-platinum compounds with the aim testing them for their interaction capacity with respect to various DNA models. We also report a synthetic route for a... (More)
- Among the metal-based anticancer drugs, cisplatin (cis-diaminedichloroplatinum(II)) is the most widely used species in therapy. Despite its clinical success, cisplatin still suffers in generating resistance, as well as being highly toxic due to poor selectivity between healthy and sick cells. By molecular design it ought to be possible to generate new cis-platinum compounds with increased selectivity and improved cellular behaviour. In this paper, we report a synthetic pathway for construction of derivatives of 1,1'-bis(diphenylphosphino)-ferrocene, together with their corresponding cis-platinum compounds with the aim testing them for their interaction capacity with respect to various DNA models. We also report a synthetic route for a nucleoside-based cis-platinum compound containing a bidentate ferrocenylphosphine derivative connected through a succinamic-based linker to the 5-position of the heterocyclic moiety of uridine. Our preliminary kinetic investigation of 5-{N-[1-[1',2-bis(diphenylphosphino)ferrocenyl]ethyl]1-N'-[prop-2-yn-3-y l]succinamide} uridinedichloroplatinum(II) showed that this compound reacted faster with the phosphorothioate containing oligonucleotides d(T(6)p(S)T-6), with an observed first-order rate constant k(obs) = (1.4 +/- 0.1) X 10(-4) s(-1), compared with the G-N7 target in d(T(7)GGT(7)), for which the observed first-order rate constant is k(obs) = (7.2 +/- 0.5) X 10(-4) s(-1). (c) 2006 Elsevier Ltd. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/410599
- author
- Bjelosevic, Haris LU ; Spegel, Christer LU ; Sykfont Snygg, Åse LU ; Gorton, Lo LU ; Elmroth, Sofi LU and Persson, Tina LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cisplatin, anticancer, kinetics, linker, nucleoside analogue, Pt(dppf)
- in
- Tetrahedron
- volume
- 62
- issue
- 18
- pages
- 4519 - 4527
- publisher
- Elsevier
- external identifiers
-
- wos:000237126200029
- scopus:33646103459
- ISSN
- 0040-4020
- DOI
- 10.1016/j.tet.2006.02.057
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240), Analytical Chemistry (S/LTH) (011001004), Biochemistry and Structural Biology (S) (000006142)
- id
- e492d6fc-c9bb-43ef-b2c8-6070c4d2183b (old id 410599)
- date added to LUP
- 2016-04-01 15:25:49
- date last changed
- 2022-01-28 05:16:15
@article{e492d6fc-c9bb-43ef-b2c8-6070c4d2183b,
abstract = {{Among the metal-based anticancer drugs, cisplatin (cis-diaminedichloroplatinum(II)) is the most widely used species in therapy. Despite its clinical success, cisplatin still suffers in generating resistance, as well as being highly toxic due to poor selectivity between healthy and sick cells. By molecular design it ought to be possible to generate new cis-platinum compounds with increased selectivity and improved cellular behaviour. In this paper, we report a synthetic pathway for construction of derivatives of 1,1'-bis(diphenylphosphino)-ferrocene, together with their corresponding cis-platinum compounds with the aim testing them for their interaction capacity with respect to various DNA models. We also report a synthetic route for a nucleoside-based cis-platinum compound containing a bidentate ferrocenylphosphine derivative connected through a succinamic-based linker to the 5-position of the heterocyclic moiety of uridine. Our preliminary kinetic investigation of 5-{N-[1-[1',2-bis(diphenylphosphino)ferrocenyl]ethyl]1-N'-[prop-2-yn-3-y l]succinamide} uridinedichloroplatinum(II) showed that this compound reacted faster with the phosphorothioate containing oligonucleotides d(T(6)p(S)T-6), with an observed first-order rate constant k(obs) = (1.4 +/- 0.1) X 10(-4) s(-1), compared with the G-N7 target in d(T(7)GGT(7)), for which the observed first-order rate constant is k(obs) = (7.2 +/- 0.5) X 10(-4) s(-1). (c) 2006 Elsevier Ltd. All rights reserved.}},
author = {{Bjelosevic, Haris and Spegel, Christer and Sykfont Snygg, Åse and Gorton, Lo and Elmroth, Sofi and Persson, Tina}},
issn = {{0040-4020}},
keywords = {{cisplatin; anticancer; kinetics; linker; nucleoside analogue; Pt(dppf)}},
language = {{eng}},
number = {{18}},
pages = {{4519--4527}},
publisher = {{Elsevier}},
series = {{Tetrahedron}},
title = {{Synthesis and structural characterisation of novel platinum-based drug candidates with extended functionality by incorporation of bis(diphenylphosphino)ferrocene units as metal chelators}},
url = {{https://lup.lub.lu.se/search/files/4390918/1224434.pdf}},
doi = {{10.1016/j.tet.2006.02.057}},
volume = {{62}},
year = {{2006}},
}