Issue 2, 2019

Esterification of the free carboxylic group from the lutidinic acid ligand as a tool to improve the cytotoxicity of Ru(ii) complexes

Abstract

In this study, we report on the selective esterification of the carboxyl group in a coordinated ligand based on the Fischer reaction. The new [Ru(N–O)(bipy)(dppb)]PF6 complex 1 was used as a precursor to obtain the ester derivative [Ru(N–Oet)(bipy)(dppb)]PF6 (2), and in order to establish the influence of either the free carboxyl group or the ethoxycarbonyl group on biological properties, the [Ru(pic)(bipy)(dppb)]PF6 complex (3) was synthesized for comparison (dppb = 1,4-bis(diphenylphosphino)butane, bipy = 2,2′-bipyridine, N–O = mono-deprotonated 2,4-pyridinedicarboxylic acid, N–Oet = 4-ethoxycarbonyl-2-pyridinecarboxylic acid). All three complexes interact weakly with human serum albumin (HSA) with Kb values ranging from 101–104 M−1, suggesting a spontaneous interaction with this protein by electrostatic (1–2) or van der Waals interactions (3). Moreover, complex/DNA-binding experiments indicate that complexes 2 and 3 interact weakly with DNA, while no interaction is observed between complex 1 and DNA, probably due to the repulsion involving the free carboxylate group/DNA-phosphate. Anti-Mycobacterium tuberculosis (MTB) activity and cytotoxicity assays against one normal cell line V79 (hamster fibroblast) and three human cancer cell lines A549 (lung), MCF7 and MDA-MB-231 (breast) revealed that complexes 2 and 3 exhibit good activity against MTB and tumor cells, presenting high cytotoxicity (low IC50). On the other hand, complex 1 is practically inactive. Therefore, the best biological results found for complex 2 can be attributed to its esterification, improving the lipophilicity and cellular uptake, in order to facilitate its passive permeation through the tumor cell membranes allowing for cell death, as well as DNA and HSA interactions, when compared with complex 1.

Graphical abstract: Esterification of the free carboxylic group from the lutidinic acid ligand as a tool to improve the cytotoxicity of Ru(ii) complexes

Supplementary files

Article information

Article type
Research Article
Submitted
04 Sep 2018
Accepted
25 Oct 2018
First published
26 Oct 2018

Inorg. Chem. Front., 2019,6, 376-390

Esterification of the free carboxylic group from the lutidinic acid ligand as a tool to improve the cytotoxicity of Ru(II) complexes

J. Honorato, L. Colina-Vegas, R. S. Correa, A. P. M. Guedes, M. Miyata, F. R. Pavan, J. Ellena and A. A. Batista, Inorg. Chem. Front., 2019, 6, 376 DOI: 10.1039/C8QI00941D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements