Antileishmanial activity of cordiaquinone E towards Leishmania (Leishmania) amazonensis

Autor(es)

Luz Rodrigues, Raiza Raianne ^[1] ; Lima Nunes, Thais Amanda ^[1] ; de Araujo, Alyne Rodrigues ^[2] ; Barreto Marinho Filho, Jose Delano ^[3] ; da Silva, Marcos Vinicius ^[4] ; de Amorim Carvalho, Fernando Aecio ^[5] ; Loiola Pessoa, Otilia Deusdenia ^[6] ; Silva Freitas, Hozana Patricia ^[6] ; da Franca Rodrigues, Klinger Antonio ^[1] ; Araujo, Ana Jersia ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Delta Parnaiba, Campus Minist Reis Velloso, Lab Doencas Infecciosas, BR-64202020 Parnaiba, PI - Brazil

^[2] Univ Fed Delta Parnaiba, Campus Minist Reis Velloso, Nucleo Pesquisa Biodiversidade & Biotecnol, BR-64202020 Parnaiba, PI - Brazil

^[3] Univ Fed Delta Parnaiba, Campus Minist Reis Velloso, Lab Cultura Celulas Delta, BR-64202020 Parnaiba, PI - Brazil

^[4] Univ Fed Triangulo Mineiro, Lab Imunol & Parasitol, Inst Ciencias Biol & Nat, BR-38025180 Uberaba, MG - Brazil

^[5] Univ Fed Piaui, Nucleo Pesquisas Plantas Med, Campus Minist Petronio Portella, BR-64049550 Teresina, Piaui - Brazil

^[6] Univ Fed Ceara, Dept Quim Organ & Inorgan, BR-60021970 Fortaleza, CE - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Immunopharmacology; v. 90, JAN 2021.
• Citações Web of Science: 0

Resumo

Leishmaniasis is caused by several protozoan species of Leishmania, and being endemically present in 98 countries around the world, it is also a severe public-health problem. The available antileishmanial drugs are toxic and yet present risks of recurrent infection. Efforts to find new, effective, and safe oral agents for the treatment of leishmaniasis are continuing throughout the world. This work aimed to evaluate the antileishmania activity of cordiaquinone E (CORe), isolated from the roots of Cordia polycephala (Lam.) I. M. Johnston. Cytotoxicity, and possible mechanisms of action against promastigote and amastigote forms of Leishmania amazonensis were examined. CORe was effective in inhibiting promastigote (IC50 4.5 +/- 0.3 mu M) and axenic amastigote (IC50 2.89 +/- 0.11 mu M) growth in concentrations found non-toxic for the host cell (CC50 246.81 +/- 14.5 mu M). Our results revealed that CORe presents direct activity against the parasite, inducing cell death by apoptosis. CORe present greater activity against intracellular amastigotes (EC50 1.92 +/- 0.2 mu M), yet with much higher selectivity indexes than the reference drugs, being respectively more benign towards RAW 264.7 macrophages than meglumine antimoniate and amphotericin B, (respectively by 4.68 and 42.84 fold). The antiamastigote activity was associated with increased TNF-alpha, IL-12, NO, and ROS levels, as well as decreased IL-10 levels. These results encourage the progression of studies on this compound for the development of new leishmanicidal agents. (AU)

• Processo FAPESP: 14/50926-0 - INCT 2014: biodiversidade e produtos naturais
• Beneficiário: Vanderlan da Silva Bolzani
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático