Biological activity of Morita-Baylis-Hillman adduct homodimers in L. infantum and L. amazonensis: anti-Leishmania activity and cytotoxicity

• Published in: Parasitology research (1987) 2019-10, Vol.118 (10), p.3067-3076
• Main Authors: da Câmara Rocha, Juliana, da Franca Rodrigues, Klinger Antonio, do Nascimento Néris, Patrícia Lima, da Silva, Larisse Virgolino, Almeida, Fernanda Silva, Lima, Viviane Silva, Peixoto, Rephany Fonseca, da Câmara Rocha, Juliene, de Azevedo, Fátima de Lourdes Assunção Araújo, Veras, Robson Cavalcanti, de Medeiros, Isac Almeida, da Silva, Wagner André Vieira, Lima-Junior, Claudio G., de Almeida Vasconcellos, Mário Luiz Araújo, do Amaral, Ian Porto Gurgel, de Oliveira, Márcia Rosa, de Souza Lima Keesen, Tatjana
• Format: Article
• Language: English
• Subjects: Adducts; Amphotericin B; Apoptosis; Biological activity; Biomedical and Life Sciences; Biomedicine; Cell death; Cutaneous leishmaniasis; Cytotoxicity; Erythrocytes; Immunology; Leishmania; Leishmaniasis; Leukocytes (mononuclear); Medical Microbiology; Microbiology; Parasitic diseases; Peripheral blood mononuclear cells; Treatment and Prophylaxis - Original Paper
• ISSN: 0932-0113; 1432-1955
• DOI: 10.1007/s00436-019-06403-w

This study is a report on the anti- Leishmania activity of Morita-Baylis-Hillman (MBH) homodimers adducts against the promastigote and axenic amastigote forms of Leishmania ( Leishmania ) infantum and Leishmania ( Leishmania ) amazonensis and on the cytotoxicity of these adducts to human blood cells. Both studied homodimers, MBH 1 and MBH 2, showed activity against the promastigote forms of L. infantum and L. amazonensis , which are responsible for visceral and cutaneous leishmaniasis, respectively. Additionally, the homodimers presented biological activity against the axenic amastigote forms of these two Leishmania species. The adducts exhibited no hemolytic activity to human peripheral blood mononuclear cells or erythrocytes at the tested concentrations and achieved higher selectivity indices than amphotericin B. Evaluation of cell death by apoptosis revealed that the homodimers had better apoptosis/necrosis profiles than amphotericin B in the promastigote forms of both L. infantum and L. amazonensis . In conclusion, these Morita-Baylis-Hillman adducts had anti- Leishmania activity in an in vitro model and may thus be promising molecules in the search for new drugs to treat leishmaniasis.