Microwave-assisted synthesis of 2-styrylquinoline-4-carboxylic acid derivatives to improve the toxic effect against Leishmania (Leishmania) amazonensis

Autor(es)

Luczywo, Ayelen ^[1] ; Sauter, Ismael Pretto ^[2] ; da Silva Ferreira, Thalita Camelo ^[2] ; Cortez, Mauro ^[2] ; Romanelli, Gustavo P. ^[3] ; Sathicq, Gabriel ^[3] ; Asis, Silvia E. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Buenos Aires, Fac Farm & Bioquim, Dept Quim Organ, Junin 956, C1113AAD, Buenos Aires, DF - Argentina

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Lab Imunobiol Interacao Leishmania Macrofagos, Ave Prof Lineu Prestes 1374, BR-05508000 Sao Paulo - Brazil

^[3] Univ Nacl La Plata, CONICET, CCT La Plata, Ctr Invest & Desarrollo Ciencias Aplicadas Dr Jor, La Plata - Argentina

• Tipo de documento: Artigo Científico
• Fonte: Journal of Heterocyclic Chemistry; v. 58, n. 3 JAN 2021.
• Citações Web of Science: 1

Resumo

The identification of new compounds is urgent to develop safe and efficacious candidates for leishmaniasis treatment, especially from natural products as a potential source of active molecules against neglected tropical parasite diseases. Inspired by the efficacious quinoline alkaloid microbial effects, we have previously reported the synthesis and biological activity of 2-phenylquinoline-4-carboxylic acids and poly-substituted quinolines against parasites. In this work, a series of eighteen 2-styryl-4-quinolinecarboxylic acids were synthesized under microwave irradiation settings obtaining from good to excellent yields (60%-90%), shorter reaction times (2 minutes), and eco-friendly experimental conditions. All these products were evaluated against infective forms of Leishmania (Leishmania) amazonensis, such as promastigotes and intracellular amastigotes, based on cytotoxicity assays, including host macrophage infection assays. Compounds 4 and 5 possessing a 2-chloro or 4-chlorostyryl moiety, respectively, were considered the most promising antileishmanial agents due to the parasite killing effect in intracellular forms inside infected macrophages. Thus, our results revealed that the 2-styryl-4-quinolinecarboxylic acid backbone structure was essential for the activity against intracellular pathogens like L. (L.) amazonensis. (AU)

• Processo FAPESP: 12/24105-3 - Imunobiologia de Leishmania spp.: estudo do papel de CD200 e biogênese do vacúolo parasitóforo em células fagocíticas infectadas por Leishmania
• Beneficiário: Mauro Javier Cortez Véliz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores