Author | Nóbrega, Flávio Roberto | |
Author | Silva, Larisse Vieira | |
Author | Bezerra Filho, Carlos da Silva Maia | |
Author | Lima, Tamires Cardoso | |
Author | Castillo, Yunierkis P. | |
Author | Bezerra, Daniel Pereira | |
Author | Lima, Tatjana K. Souza | |
Author | Sousa, Damião Pereira de | |
Access date | 2019-02-19T16:30:11Z | |
Available date | 2019-02-19T16:30:11Z | |
Document date | 2019 | |
Citation | NÓBREGA, F. R. et al. Design, Antileishmanial Activity, and QSAR Studies of a Series of Piplartine Analogues. Journal of Chemistry, p. 1-13, 2019. | pt_BR |
ISSN | 2090-9063 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/31766 | |
Sponsorship | Brazilian agencies Conselho
Nacional de Desenvolvimento Cient´ıfico e Tecnol´ogico
(CNPq) and Coordenação de Aperfeiçoamento de Pessoal de
N´ıvel Superior (CAPES) | pt_BR |
Language | eng | pt_BR |
Publisher | Hindawi Publishing Corporation | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmaniose | pt_BR |
Subject in Portuguese | Leishmaniose visceral | pt_BR |
Subject in Portuguese | Drogas | pt_BR |
Subject in Portuguese | Avaliação de Medicamentos | pt_BR |
Subject in Portuguese | Piper | pt_BR |
Title | Design, Antileishmanial Activity, and QSAR Studies of a Series of Piplartine Analogues | pt_BR |
Type | Article | pt_BR |
DOI | 10.1155/2019/4785756 | pt_BR |
Abstract | Piplartine is an alkamide found in different Piper species and possesses several biological activities, including antiparasitic properties. Thus, the aim of the present study was to evaluate a series of 32 synthetic piplartine analogues against the Leishmania amazonensis promastigote forms and establish the structure-activity relationship and 3D-QSAR of these compounds. The antileishmanial effect of the compounds was determined using the MTTmethod. Most compounds were found to be active against L. amazonensis. Among 32 assayed derivatives, compound (E)-(−)-bornyl 3-(3,4,5-trimethoxyphenyl)-acrylate exhibited the most potent antileishmanial activity (IC50 = 0.007 ± 0.008 μM, SI > 10), followed by benzyl 3,4,5-trimethoxybenzoate (IC50 = 0.025 ± 0.009 μM, SI > 3.205) and (E)-furfuryl
3-(3,4,5-trimethoxyphenyl)-acrylate (IC50 = 0.029 ± 0.007 μM, SI > 2.688). It was found that the rigid substituents contribute to increasing antiparasitic activity against L. amazonensis promastigotes. The presence of the unsaturated heterocyclic substituent in the phenylpropanoid chemical structure (furfuryl group) resulted in a bioactive derivative. Molecular simplification of benzyl 3,4,5- trimethoxybenzoate by omitting the spacer group contributed to the bioactivity of this compound. Furthermore, bornyl radical appears to be important for antileishmanial activity, since (E)-(−)-bornyl 3-(3,4,5-trimethoxyphenyl)-acrylate exhibited the most potent antileishmanial activity. These results show that some derivatives studied would be useful as prototype molecules for the planning of new derivatives with profile of antileishmanial drugs. | pt_BR |
Affilliation | Universidade Federal da Paraíba. Laboratory of Pharmaceutical Chemistry. João Pessoa, PB, Brazil. | pt_BR |
Affilliation | Universidade Federal da Paraíba. Department of Cellular and Molecular Biology. João Pessoa, PB, Brazil. | pt_BR |
Affilliation | Universidade Federal da Paraíba. Laboratory of Pharmaceutical Chemistry. João Pessoa, PB, Brazil. | pt_BR |
Affilliation | Federal University of Sergipe. Department of Pharmacy. São Cristóvão, SE, Brazil. | pt_BR |
Affilliation | Universidad de Las Américas. Escuela de Ciencias Físicas y Matemáticas. Quito, Ecuador. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal da Paraíba. Department of Cellular and Molecular Biology. João Pessoa, PB, Brazil. | pt_BR |
Affilliation | Universidade Federal da Paraíba. Laboratory of Pharmaceutical Chemistry. João Pessoa, PB, Brazil. | pt_BR |
Subject | Leishmaniasis | pt_BR |
Subject | Visceral leishmaniasis | pt_BR |
Subject | Drugs | pt_BR |
Subject | Drug Evaluation | pt_BR |
Subject | Piper | pt_BR |