Antibacterial and Antileishmanial Activity of 1,4-Dihydropyridine Derivatives.

Autor: Oliveira TAS; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., Silva JBA; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., Silva NBS; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Félix PCA; Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, SP, Brazil., Dos Santos DA; Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, SP, Brazil., de Oliveira AM; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Martins CHG; Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil., Magalhães LG; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil., Crotti AEM; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Sep 04, pp. e202401300. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1002/cbdv.202401300
Abstrakt: We have synthesized twenty-three 1,4-dihydropyridine derivatives (1,4-DHPs) by using a microwave-assisted one-pot multicomponent Hantzsch reaction and evaluated their antibacterial activity against a representative panel of cariogenic bacteria and their in vitro antileishmanial activity against Leishmania (L.) amazonensis promastigotes and amastigotes. Thirteen compounds were moderately active against Streptococcus sanguinis, Streptococcus mitis, and Lactobacillus paracasei. Compound 22 (diethyl 4-(3-methoxy-4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) displayed moderate antibacterial activity against S. mitis and S. sanguinis, with a Minimum Inhibitory Concentration (MIC) of 500 μg/mL); compounds 8 (ethyl 2,7,7-trimethyl-4-(3-chlorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) and 10 (ethyl 2,7,7-trimethyl-4-(3-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were moderately active against S. sanguinis (MIC=500 μg/mL) and very active against L. amazonensis promastigotes (IC 50 =43.08 and 34.29 μM, respectively). Among the eight 1,4-DHPs that were active (IC 50 <50 μM) against L. amazonensis promastigotes, compound 13 (ethyl 2,7,7-trimethyl-4-(3,4,5-trimethoxyphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) was the most active (IC 50 =24.62 μM) and had a Selectivity Index (SI) higher than 4 compared to GM07492 A cells. On the other hand, compounds 7 (ethyl 2,7,7-trimethyl-4-(3-fluorophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) and 9 (ethyl 2,7,7-trimethyl-4-(2-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) were the most active against L. amazonensis amastigotes (IC 50 =12.53 and 13.67 μM, respectively; SI>7.9 and >7.3, respectively) after 24 h of treatment. Our results indicated that asymmetric 1,4-DHPs derived from dimedone exhibit antileishmanial potential.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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