Leishmanicidal activity of Morita-Baylis–Hillman adducts

• Published in: Parasitology research (1987) 2022-02, Vol.121 (2), p.751-762
• Main Authors: Vieira, Ana Carolina Santana, da Silva Santos, Mariana, Leite, Anderson Brandão, da Silva, Amanda Evelyn, Cavalcante-Silva, Luiz Henrique Agra, de Souza Augusto Pereira, Gabrielle, Marques, Sany Delany Gomes, de Oliveira Santos, Barbara Viviana, Duarte, Alysson Wagner Fernandes, de Queiroz, Aline Cavalcante, de Luna-Freire, Kristerson Reinaldo, Alexandre-Moreira, Magna Suzana
• Format: Article
• Language: English
• Subjects: Adducts; Amastigotes; Antiprotozoal Agents - toxicity; Biomedical and Life Sciences; Biomedicine; Carboxylic acids; Cytotoxicity; Developing countries; Hepatotoxicity; Humans; Immunology; LDCs; Leishmaniasis; Leishmaniasis - drug therapy; Macrophages; Medical Microbiology; Microbiology; Organic Chemicals; Pancreatitis; Parasitic diseases; Pentamidine isethionate; Phenylpropanoids; Promastigotes; Public health; Treatment and Prophylaxis - Original Paper
• ISSN: 0932-0113; 1432-1955
• DOI: 10.1007/s00436-021-07421-3

Leishmaniasis is a neglected disease that affects millions of people, mostly in developing countries. Although this disease has a high impact on public health, there are few drug options to treat the different leishmaniasis forms. Additionally, these current therapies have various adverse effects, including gastrointestinal disturbances, headache, pancreatitis, and hepatotoxicity. Thus, it is essential to develop new drug prototypes to treat leishmaniasis. Accordingly, the present study aimed to evaluate the leishmanicidal activity of Morita-Baylis–Hillman adducts and their O-acetylates, carboxylic acid derivatives, and acid and ester derivatives of 2-methyl-phenylpropanoids against Leishmania chagasi . Initially, we evaluated the cytotoxicity of 16 derivatives (1-16G) against J774A.1 macrophages. Eight derivatives (2G, 4G, 5G, 7G, 9G, 10G, 13G, and 15G) showed no cytotoxicity at up to the maximum concentration tested (100 μM). When evaluated for antileishmanial effect against promastigote forms, 1G, 6G, 8G, 10G, 11G, 13G, 14G, 15G, and 16G displayed significant toxicity compared to the control (0.1% DMSO). Additionally, the compounds 1G, 5G, 7G, 9G, 11G, 13G, 14G, and 16G reduced macrophage infection by amastigotes. Thus, we conclude that these derivatives have antileishmanial effects, particularly 1G, which showed activity against promastigotes and amastigotes, and low toxicity against macrophages.