Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas conjugated to polyamine scaffolds

Authors

Tameryn Stringer, University of Cape Town
Dale Taylor, University of Cape Town Medical School,
Carmen de Kock, University of Cape Town Medical School
Hajira Guzgay, University of the Pacific
Aaron Au, University of the Pacific
Seung Hwan An, University of the Pacific
Benjamin Sanchez, University of the Pacific
Raquel O'Connor, University of the Pacific
Neal Patel, Unversity of the Pacific
Kirkwood M. Land, University of the PacificFollow
Peter J. Smith, University of Cape Town Medical School
Denver T. Hendricks, University of Cape Town
Timothy J. Egan, University of Cape Town
Gregory S. Smith, University of Cape TownFollow

ORCID

Kirkwood M. Land: 0000-0001-5951-9630

Document Type

Article

Publication Title

European Journal of Medicinal Chemistry

Department

Biological Sciences

ISSN

0223-5234

Volume

69

DOI

10.1016/j.ejmech.2013.08.004

First Page

90

Last Page

98

Publication Date

11-1-2013

Abstract

A series of mono- and multimeric 4-amino-7-chloroquinoline and ferrocenyl thioureas have been prepared by the reaction of a 7-chloroquinoline methyl ester and a ferrocenylimine methyl ester with various amines. These compounds were characterized using standard spectroscopic and analytical techniques. The compounds were evaluated against the NF54 (CQ-sensitive) and Dd2 (CQ-resistant) strains of Plasmodium falciparum. The quinoline compounds show enhanced activity compared to the ferrocene compounds against this parasite. Compound 5 displays the most promising activity against the NF54 strain. Compounds 5 and 6 are effective at inhibiting β-hematin formation perhaps due to an increased number of quinoline moieties. The trimeric (12) and tetrameric (13) ferrocenyl compounds also inhibit β-hematin formation, albeit to a lesser degree compared to the quinoline thioureas. The compounds were also screened against the G3 strain of Trichomonas vaginalis and here the ferrocene-containing compounds show a slightly higher parasite growth inhibition compared to the quinoline thioureas. The quinoline compounds were also found to be more cytotoxic compared to the ferrocenyl compounds. Compound 6 displays good cytotoxicity against WHCO1 oesophageal cancer cells.

Recommended Citation

Stringer, T., Taylor, D., de Kock, C., Guzgay, H., Au, A., Hwan An, S., Sanchez, B., O'Connor, R., Patel, N., Land, K. M., Smith, P. J., Hendricks, D. T., Egan, T. J., & Smith, G. S. (2013). Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas conjugated to polyamine scaffolds. European Journal of Medicinal Chemistry, 69, 90–98. DOI: 10.1016/j.ejmech.2013.08.004
https://scholarlycommons.pacific.edu/cop-facarticles/771