1703-35-1Relevant academic research and scientific papers
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)
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
Rapid access to cinnamamides and piper amides: Via three component coupling of arylaldehydes, amines, and Meldrum's acid
Ghosh, Santanu,Jana, Chandan K.
supporting information, p. 5803 - 5807 (2019/11/11)
A practical method for the synthesis of cinnamamides and piper amides via a conceptually novel three component reaction of aldehydes, amines and Meldrum's acid has been reported. The reaction proceeds under operationally simple conditions without the aid of coupling reagents, oxidants, or catalysts, which are essential for the preparation of cinnamamides/piper amides via known methods. The formation of undesired chemical wastes that generally originate from the use of coupling reagents, oxidants, or catalysts has been avoided to make this reaction more atom economical.
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.
Design, Antileishmanial Activity, and QSAR Studies of a Series of Piplartine Analogues
Nóbrega, Flávio R.,Silva, Larisse V.,Bezerra Filho, Carlos Da Silva M.,Lima, Tamires C.,Castillo, Yunierkis P.,Bezerra, Daniel P.,Lima, Tatjana K. Souza,Sousa, Dami?o P. De
, (2019/01/30)
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 MTT method. 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.
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.
Synthesis and Evaluation of a Series of 3,4,5-Trimethoxycinnamic Acid Derivatives as Potential Antinarcotic Agents
Jung, Jae-Chul,Moon, Sohyeon,Min, Dongguk,Park, Woo Kyu,Jung, Mankil,Oh, Seikwan
, p. 389 - 398 (2013/04/10)
A series of 3,4,5-trimethoxycinnamic acid derivatives was prepared and evaluated for antinarcotic effects on morphine dependence in mice and binding affinities on serotonergic receptors. The key synthetic strategies involve generation of ketones 6-7, esters 9-12 through condensation reaction, and amides 13-19 via coupling reaction using 1-hydroxybenzotriazole/ethyl(dimethylaminopropryl)carbodiimide system in high yield. We found that the naloxone-induced morphine withdrawal syndrome was significantly suppressed by new synthetic 3,4,5-trimethoxycinnamic acid derivatives (20mg/kg/day). Most of 3,4,5-trimethoxycinnamic acid derivatives were found to have high affinity to 5-HT1A receptor. The naloxone-induced morphine withdrawal syndrome was attenuated by (+)8-OH-DPAT (0.1mg/kg/day, i.p.), a 5-HT1A receptor agonist. In cortical neuronal cells, (+)8-OH-DPAT (1μm) produced an elevation of the pERK 1/2 expression, and the elevated pERK levels were inhibited by WAY 100635, a 5-HT1A receptor-specific antagonist. Interestingly, the pERK levels were increased by the 3,4,5-trimethoxycinnamic acid derivatives and the derivatives-mediated changes in pERK levels were blocked by the WAY 100635. These results suggested that new synthetic 3,4,5-trimethoxycinnamic acid derivatives have a potential antinarcotic effect through acting as a 5-HT1A receptor agonist in mice.
Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)
Rao, Vidadala Ramasubba,Muthenna, Puppala,Shankaraiah, Gundeti,Akileshwari, Chandrasekhar,Babu, Kothapalli Hari,Suresh, Ganji,Babu, Katragadda Suresh,Chandra Kumar, Rotte Sateesh,Prasad, Kothakonda Rajendra,Yadav, Potharaju Ashok,Petrash, J. Mark,Reddy, Geereddy Bhanuprakash,Rao, Janaswamy Madhusudana
, p. 344 - 361 (2013/01/15)
As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC50 of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells.
