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Novel Hydrophilic Riminophenazines as Potent Antiprotozoal Agents
Author(s) -
Bassanini Ivan,
Parapini Silvia,
Basilico Nicoletta,
Sparatore Anna
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900522
Subject(s) - antiprotozoal , cytotoxicity , amastigote , plasmodium falciparum , protozoa , leishmania , leishmania major , in vitro , biochemistry , chemistry , chloroquine , biology , substituent , leishmaniasis , ic50 , stereochemistry , pharmacology , microbiology and biotechnology , parasite hosting , malaria , immunology , world wide web , computer science
Abstract SAR studies on a set of novel hydrophilic C‐2 aminopyridinyl riminophenazines bearing variously functionalized basic side chains at C‐3 were conducted. The novel compounds were evaluated for in vitro activity against two different species of Leishmania promastigotes, intramacrophage Leishmania amastigotes, chloroquine‐sensitive and chloroquine‐resistant strains of P. falciparum , and also against mature‐stage P. falciparum gametocytes. Their cytotoxicity was evaluated as well on BMDM cell lines. Most of the new compounds potently inhibited the growth of both genera of protozoa with IC 50 values in the high nanomolar range and good selectivities versus mammalian cells. Besides their potent activity against asexual intraerythrocytic stages of P. falciparum , three compounds showed potential as transmission‐blocking agents. The key role of the hydrophilic C‐2 aminopyridinyl substituent to improve the leishmanicidal activity and the influence of the length and the nature of the basic side chain on the antiprotozoal activity and cytotoxicity were underlined.