Tetraazamacrocyclic derivatives and their metal complexes as antileishmanial leads

Several bis-aryl-monocyclic polyamines and their metal complexes were shown to be potent in vitro inhibitors of Leishmania donovani. The synthesis of the two most promising compounds, FeL7Cl2 and MnL7Cl2, are shown below. [Display omitted] A total of 44 bis-aryl-monocyclic polyamines, monoaryl-monoc...

Full description

Saved in:

Bibliographic Details
Published in:	Polyhedron Vol. 163; pp. 42 - 53
Main Authors:	Hubin, Timothy J., Walker, Ashlie N., Davilla, Dustin J., Carder Freeman, TaRynn 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.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-05-2019
Subjects:	Antileishmanial drug lead Cyclam Cyclen Metal complexes Polyamine Polyamine Cyclen Antileishmanial drug lead Metal complexes Cyclam metal complexes polyamine cyclam antileishmanial drug lead
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Several bis-aryl-monocyclic polyamines and their metal complexes were shown to be potent in vitro inhibitors of Leishmania donovani. The synthesis of the two most promising compounds, FeL7Cl2 and MnL7Cl2, are shown below. [Display omitted] 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 IC50 and/or IC90 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 IC50 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 (FeL7Cl2 and MnL7Cl2), with strong activity against both promastigotes and amastigotes and no observable toxicity against the THP1 cells are the Fe2+- and Mn2+-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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0277-5387 1873-3719
DOI:	10.1016/j.poly.2019.02.027