Novel Hydrophilic Riminophenazines as Potent Antiprotozoal Agents.
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.
['Bassanini|Ivan|I|0000-0001-9589-3689', 'Parapini|Silvia|S|', 'Basilico|Nicoletta|N|', 'Sparatore|Anna|A|0000-0003-2135-2649']
D000818:Animals D000981:Antiprotozoal Agents D002460:Cell Line D002991:Clofazimine D004305:Dose-Response Relationship, Drug D057927:Hydrophobic and Hydrophilic Interactions D018314:Leishmania infantum D007895:Leishmania tropica D008264:Macrophages D051379:Mice D015394:Molecular Structure D021261:Parasitic Sensitivity Tests D013329:Structure-Activity Relationship
riminophenazines antileishmanial activity antiplasmodial activity clofazimine