Evaluation on the leishmanicidal activity of 2-N,N'-dialkylamino-1,4-naphthoquinone derivatives.
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.
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil. Electronic address: morgana_vital@hotmail.com.
Morgana V
MV
de Araújo
Laboratory of Bioactive Compounds Synthesis, Molecular Sciences Department, Federal Rural University of Pernambuco, 52171-900, Recife, PE, Brazil. Electronic address: cibelle.cabral@gmail.com.
Cibelle Cabral
CC
David
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil. Electronic address: Zeca_1989@hotmail.com.
José Clementino
JC
Neto
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil. Electronic address: luizpldeoliveira@gmail.com.
Luiz A P L
LA
de Oliveira
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil. Electronic address: karol.jatobas@gmail.com.
Karoline Cristina Jatobá
KC
da Silva
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil. Electronic address: migueljeffersonjm@gmail.com.
Jefferson Miguel
JM
Dos Santos
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil.
João Kayke S
JK
da Silva
Laboratory of Bioactive Compounds Synthesis, Molecular Sciences Department, Federal Rural University of Pernambuco, 52171-900, Recife, PE, Brazil. Electronic address: vic_aragao@hotmail.com.
Victoria B C
VB
de A Brandão
Laboratory of Bioactive Compounds Synthesis, Molecular Sciences Department, Federal Rural University of Pernambuco, 52171-900, Recife, PE, Brazil. Electronic address: sarmentosilva@gmail.com.
Tania M S
TM
Silva
Laboratory of Bioactive Compounds Synthesis, Molecular Sciences Department, Federal Rural University of Pernambuco, 52171-900, Recife, PE, Brazil. Electronic address: ccelso@gmail.com.
Celso A
CA
Camara
Laboratory of Pharmacology and Immunity, Institute of Biological Sciences and Health, Federal University of Alagoas, 57020-720, Maceió, AL, Brazil. Electronic address: suzana.magna@gmail.com.
Magna S
MS
Alexandre-Moreira
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010419:Pentamidine / Q000494:pharmacology / Q000633:toxicity
D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D010419:Pentamidine
L. amazonensis; L. chagasi; Leishmaniasis; Naphthoquinone