title: Neolignan Licarin A presents effect against Leishmania (Leishmania) major associated with immunomodulation in vitro.
abstract: Leishmaniasis' treatment is based mostly on pentavalent antimonials or amphotericin B long-term administration, expensive drugs associated with severe side effects. Considering these aforementioned, the search for alternative effective and safe leishmaniasis treatments is a necessity. This work evaluated a neolignan, licarin A anti-leishmanial activity chemically synthesized by our study group. It was observed that licarin A effectively inhibited Leishmania (Leishmania) major promastigotes (IC₅₀ of 9.59 ± 0.94 μg/mL) growth, by inducing in these parasites genomic DNA fragmentation in a typical death pattern by apoptosis. Additionally, the neolignan proved to be even more active against intracellular amastigotes of the parasite (EC₅₀ of 4.71 ± 0.29 μg/mL), and significantly more effective than meglumine antimoniate (EC₅₀ of 216.2 ± 76.7 μg/mL) used as reference drug. The antiamastigote activity is associated with an immunomodulatory activity, since treatment with licarin A of the infected macrophages induced a decrease in the interleukin (IL)-6 and IL-10 production. This study demonstrates for the first time the antileishmanial activity of licarin A and suggests that the compound may be a promising in the development of a new leishmanicidal agent.
authors.affiliation: Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Departamento de Biologia Molecular, Laboratório de Leishmanioses, João Pessoa, Paraíba, Brazil.
authors.forename: Patrícia L N
authors.initials: PL
authors.lastname: Néris
authors.forename: John P A
authors.initials: JP
authors.lastname: Caldas
authors.forename: Yara K S
authors.initials: YK
authors.lastname: Rodrigues
authors.forename: Francianne M
authors.initials: FM
authors.lastname: Amorim
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Leite
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodrigues-Mascarenhas
authors.forename: José M
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.forename: Luis C
authors.initials: LC
authors.lastname: Rodrigues
authors.forename: Márcia R
authors.initials: MR
authors.lastname: Oliveira
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D018320:Leishmania major / Q000187:drug effects* / Q000235:genetics; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D017705:Lignans / Q000494:pharmacology* / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology / Q000633:toxicity; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines; D007155:Immunologic Factors; D017705:Lignans; D009942:Organometallic Compounds; C432503:licarin A; D009569:Nitric Oxide; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000666:Amphotericin B
keywords: Cytotoxicity; IL-10; IL-6; Leishmania (Leishmania) major; Licarin A; Macrophage