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

Tameryn Stringer, Dale Taylor, Carmen de Kock, Hajira Guzgay, Aaron Au, Seung Hwan An, Benjamin Sanchez, Raquel O'Connor, Neal Patel, Kirkwood M. Land, Peter J. Smith, Denver T. Hendricks, Timothy J. Egan, Gregory S. Smith

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume69
Early online date10 Aug 2013
DOIs
Publication statusPublished - Nov 2013

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