886989-88-4Relevant articles and documents
In silico evaluation and in vitro growth inhibition of Plasmodium falciparum by natural amides and synthetic analogs
Fokoue, Harold Hilarion,Kato, Massuo Jorge,Kuehn, Christian Collins,Teles, Carolina Bioni Garcia,Veloso, Márcia Paranho,da Silva, Minelly Azevedo,de Matos Passarini, Guilherme,de Souza Reis, Kassius,do Nascimento Martinez, Leandro,dos Santos, Ana Paula de Azevedo
, (2020/05/13)
Malaria, caused by protozoa of the genus Plasmodium, is a disease that infects hundreds of millions of people annually, causing an enormous social burden in many developing countries. Since current antimalarial drugs are starting to face resistance by the
First mechanosynthesis of piperlotines A, C, and derivatives through solvent-free Horner–Wadsworth–Emmons reaction
Ramírez-Marroquín, Oscar Abelardo,Manzano-Pérez, Flavio,López-Torres, Adolfo,Hernández-López, Alejandro,Cortés-Pacheco, Abimelek,Reyes-González, Miguel Angel
, p. 244 - 255 (2019/01/22)
Piperlotines are natural products characterized by an α,β-unsaturated amide moiety. These compounds found wide applications in Medicinal Chemistry like antibacterials, cytotoxic agents, anticoagulants, among others. To date, diverse methods of synthesis have been reported for piperlotines, but involving the use of catalysts, hazard reagents, anhydrous media or coupling reagents. Thus, in this work, we developed a greener method of synthesis of piperlotines A, C, and derivatives, through mechanochemical activation under solvent-free conditions. The reaction of a β-amidophosphonate, K2CO3, and an aromatic aldehyde afforded target compounds in moderate to good yields (46–77%), in an open atmosphere by grinding. It is worth to mention that this mechanochemical process was under thermodynamic control because just E isomer was isolated for every reaction. Moreover, synthesized piperlotines have been predicted by means of chemoinformatic analysis as potential therapeutic agents for the treatment of arthritis or cancer.
Structure–Activity relationship of piplartine and synthetic analogues against schistosoma mansoni and cytotoxicity to mammalian cells
Campelo, Yuri,Ombredane, Alicia,Vasconcelos, Andreanne G.,Albuquerque, Lucas,Moreira, Daniel C.,Plácido, Alexandra,Rocha, Jefferson,Fokoue, Harold Hilarion,Yamaguchi, Lydia,Mafud, Ana,Mascarenhas, Yvonne P.,Delerue-Matos, Cristina,Borges, Tatiana,Joanitti, Graziella A.,Arcanjo, Daniel,Kato, Massuo J.,Kuckelhaus, Selma A. S.,Silva, Marcos P. N.,de Moraes, Josué,Leite, José Roberto S. A.
, (2018/06/27)
Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several Piper species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure–function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against Schistosoma mansoni adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against S. mansoni at low concentrations (5–10 μM), but its analogues did not. In contrast, based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, piplartine exhibited toxicity in mammalian cells at 785 μM, while its analogues 19A and 6B did not reduce cell viability at the same concentrations. This study demonstrated that piplartine analogues showed less activity against S. mansoni but presented lower toxicity than piplartine.
