Tetraazamacrocyclic Derivatives and Their Metal Complexes As Antileishmanial Leads

Overview

Journal Polyhedron

Date 2019 Apr 13

PMID 30976133

Citations 7

Authors

Timothy J Hubin

Ashlie N Walker

Dustin J Davilla

TaRynn N Carder Freeman

Brittany M Epley

Travis R Hasley

Prince N A Amoyaw

Surendra Jain

Stephen J Archibald

Timothy J Prior

Jeanette A Krause

Allen G Oliver

Babu L Tekwani

M Omar F Khan

Affiliations

Soon will be listed here.

Abstract

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 promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells. The IC and/or IC 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 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 (FeCl and MnCl), with strong activity against both promastigotes and amastigotes and no observable toxicity against the THP1 cells are the Fe- and Mn- 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.

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