Evaluation on the leishmanicidal activity of 2-N,N′-dialkylamino-1,4-naphthoquinone derivatives

• Published in: Experimental parasitology Vol. 176; pp. 46 - 51
• Main Authors: de Araújo, Morgana V., David, Cibelle Cabral, Neto, José Clementino, de Oliveira, Luiz A.P.L., da Silva, Karoline Cristina Jatobá, dos Santos, Jefferson Miguel, da Silva, João Kayke S., de A Brandão, Victoria B.C., Silva, Tania M.S., Camara, Celso A., Alexandre-Moreira, Magna S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2017
• Subjects: Animals; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Inhibitory Concentration 50; L. amazonensis; L. chagasi; Leishmania mexicana - drug effects; Leishmaniasis; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - parasitology; Mice; Naphthoquinone; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Naphthoquinones - toxicity; Pentamidine - pharmacology; Pentamidine - toxicity; L. amazonensis; L. chagasi; Leishmaniasis; Naphthoquinone
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2017.02.004

Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. In this study was evaluated in vitro leishmanicidal activity of 2-N,N’-dialkylamino-1,4-naphthoquinone derivatives, covering a series of fourteen 2-N-morpholino-, 2-N-thiomorpholino, 2-N-piperidino, 2-N-(N4-methyl)-piperazino naphthoquinones (1a-n) derived from nor-lapachol and lawsone, belong to some other di-alkyaminoderivatives. At the cytotoxicity assay on peritoneal macrophages, the compounds possessing larger alkyl groups and N-methyl-piperazino moiety (1d, 1h, 1i and 1k), showed toxic effects similar to the standard drug used pentamidine. However, the other compounds of the series showed no deleterious effect on the host cell. Meanwhile, these cytotoxic derivatives (1d, 1h and 1i) had pronounced leishmanicidal activity against L. amazonensis promastigotes, and treatments with six other compounds (1d, 1e, 1f, 1h, 1k and 1n) had significant effect leishmanicidal against L. chagasi promastigotes. In the assay against L. chagasi amastigotes, eight compounds (1a, 1b, 1c, 1d, 1h, 1i, 1k and 1m) showed significant activity. Moreover, the compounds (1a, 1b, 1c, and 1m) showed effect against amastigotes of L. chagasi and not being toxic to the host cell. These data show the derivatives as promising substances for research leishmanicidal activity. [Display omitted] •We detect the naphthoquinones derivatives not present cytotoxic activity against mammaliam cells.•We identified four compounds with activity against amastigotes forms without toxic effect on mammalian cells.•The data shed new light on development of drug new for leishmaniose an important neglected disease.