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 IC50 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.
Novel Hydrophilic Riminophenazines as Potent Antiprotozoal Agents / I. Bassanini, S. Parapini, N. Basilico, A.C. Sparatore. - In: CHEMMEDCHEM. - ISSN 1860-7187. - 14:22(2019 Nov 20), pp. 1940-1949.
|Titolo:||Novel Hydrophilic Riminophenazines as Potent Antiprotozoal Agents|
BASSANINI, IVAN (Primo)
PARAPINI, SILVIA (Secondo)
SPARATORE, ANNA CONCETTINA (Ultimo) (Corresponding)
|Parole Chiave:||riminophenazines; clofazimine; antiplasmodial activity; antileishmanial activity|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore CHIM/06 - Chimica Organica
|Progetto:||PIANO DI SOSTEGNO ALLA RICERCA 2015-2017 - LINEA 2 "DOTAZIONE ANNUALE PER ATTIVITA' ISTITUZIONALE"|
|Data di pubblicazione:||20-nov-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/cmdc.201900522|
|Appare nelle tipologie:||01 - Articolo su periodico|