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Tetraazamacrocyclic derivatives and their metal complexes as antileishmanial leads

Hubin, Timothy J.; Walker, Ashlie N.; Davilla, Dustin J.; Carder Freeman, Ta Rynn N.; Epley, Brittany M.; Hasley, Travis R.; Amoyaw, Prince N.A.; Jain, Surendra; Archibald, Stephen J.; Prior, Timothy J.; Krause, Jeanette A.; Oliver, Allen G.; Tekwani, Babu L.; Khan, M. Omar F.


Timothy J. Hubin

Ashlie N. Walker

Dustin J. Davilla

Ta Rynn N. Carder Freeman

Brittany M. Epley

Travis R. Hasley

Prince N.A. Amoyaw

Surendra Jain

Jeanette A. Krause

Allen G. Oliver

Babu L. Tekwani

M. Omar F. Khan


© 2019 A total of 44 bis-aryl-monocyclic polyamines, monoaryl-monocyclic polyamines and their transition metal complexes were prepared, chemically characterized, and screened in vitro against the Leishmania donovani promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells. The IC 50 and/or IC 90 values showed that 10 compounds were similarly active at about 2-fold less potent than known drug pentamidine against promastigotes. The most potent compound had an IC 50 of 2.82 µM (compared to 2.93 µM for pentamidine). Nine compounds were 1.1–13.6-fold more potent than pentamidine against axenic amastigotes, the most potent one being about 2-fold less potent than amphotericin B. Fourteen compounds were about 2–10 fold more potent than pentamidine, the most potent one is about 2-fold less potent than amphotericin B against intracellular amastigotes in THP1 cells. The 2 most promising compounds (FeL7Cl 2 and MnL7Cl 2 ), with strong activity against both promastigotes and amastigotes and no observable toxicity against the THP1 cells are the Fe 2+ - and Mn 2+ -complexes of a dibenzyl cyclen derivative. Only 2 of the 44 compounds showed observable cytotoxicity against THP1 cells. Tetraazamacrocyclic monocyclic polyamines represent a new class of antileishmanial lead structures that warrant follow up studies.

Journal Article Type Article
Publication Date May 1, 2019
Journal Polyhedron
Print ISSN 0277-5387
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 163
Pages 42-53
APA6 Citation Hubin, T. J., Walker, A. N., Davilla, D. J., Carder Freeman, T. R. N., Epley, B. M., Hasley, T. R., …Khan, M. O. F. (2019). Tetraazamacrocyclic derivatives and their metal complexes as antileishmanial leads. Polyhedron, 163, 42-53.
Keywords Cyclen; Cyclam; Polyamine; Antileishmanial drug lead; Metal complexes
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Copyright Statement
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license

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