Study of New Ferrocene Incorporated N,N′-Disubstituted Thioureas as Potential Antitumour Agents
Bhajan Lal A B C , Amin Badshah A F , Ataf Ali Altaf D , Muhammad Nawaz Tahir E , Shafiq Ullah A and Fazlul Huq B F
+ Author Affiliations
- Author Affiliations
A Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
B Discipline of Biomedical Sciences, The University of Sydney, Sydney, NSW 1825, Australia.
C Department of Chemistry, Shah Abdul Latif University, Khairpur, Pakistan.
D Department of Chemistry, Bahauddin Zakariya University, Sub-Campus, Sahiwal, 57000, Pakistan.
E Department of Physics, University of Sargodha, Sargodha, Pakistan.
F Corresponding authors. Email: aminbadshah@yahoo.com; Fazlul.Huq@sydney.edu.au
Australian Journal of Chemistry 66(11) 1352-1360 https://doi.org/10.1071/CH13268
Submitted: 27 May 2013 Accepted: 24 June 2013 Published: 25 July 2013
Abstract
In this paper, we report the synthesis, structural characterisation, cytotoxicity against human ovarian tumour models (A2780, A2780cisR, and A2780ZD0473R), nature of interaction with calf-thymus (CT)-DNA and pBR322 plasmid DNA of new ferrocene based N,N′-disubstituted thioureas (3a–d). The compounds, characterized based on elemental analysis, FT-IR and multinuclear (1H and 13C) NMR spectroscopy, and single crystal X-ray diffractometry, were found to have significant antitumour activity although much less than cisplatin. Crystallographic data reveals the existance of secondary interactions for compound 3c in terms of intermolecular hydrogen bonding of type NH⋯O, NH⋯S and secondary non-covalent interactions (π⋯H). When pBR322 plasmid DNA was interacted with increasing concentrations of compounds, 3a and 3b but not 3c were found to partially prevent BamH1 digestion of the DNA. The negative shift in peak potential in voltammetric measurements indicates that all the compounds undergo electrostatic interactions with the negatively charged phosphate DNA backbone. The large negative value of the binding energy indicates the spontaneity of reaction between the compounds and CT-DNA and the conformational stability of adducts formed.
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