Synthesis and Antimalarial Activity of 1,4-Disubstituted Piperidine Derivatives

Seck, Rokhyatou; Gassama, Abdoulaye; Cojean, Sandrine; Cavé, Christian

doi:10.3390/molecules25020299

Cited by 21 publications

(10 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other indole compounds are antiplasmodial agents. For example, aminoindole ( 43 ), bisindole ( 44 ), piperidine indole ( 45 ), or spiroindolone ( 46 ) are known as scaffolds in the novel chemical classes of antiplasmodial agents exhibiting various modes of action, of which, aiming at the formation of hemozoin in Plasmodium falciparum , PfATP4 and melatonin receptor are the most commonly recognized modes of actions ( 47 ). Therefore, we evaluated whether ICOOH has any direct effect on sporozoite of E. maxima .…”

Section: Resultsmentioning

confidence: 99%

Gut Microbiota-Derived Indole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima

et al. 2022

View full text Add to dashboard Cite

Two studies were conducted to evaluate the effects of indole-3-carboxylate (ICOOH) as a postbiotic on maintaining intestinal homeostasis against avian coccidiosis. In the first study, an in vitro culture system was used to investigate the effects of ICOOH on the proinflammatory cytokine response of chicken macrophage cells (CMCs), gut integrity of chicken intestinal epithelial cells (IECs), differentiation of quail muscle cells (QMCs), and primary chicken embryonic muscle cells (PMCs) and anti-parasitic effect against Eimeria maxima. Cells to be tested were seeded in the 24-well plates and treated with ICOOH at concentrations of 0.1, 1.0, and 10.0 µg. CMCs were first stimulated by lipopolysaccharide (LPS) to induce an innate immune response, and QMCs and PMCs were treated with 0.5% and 2% fetal bovine serum, respectively, before they were treated with ICOOH. After 18 h of incubation, cells were harvested, and RT-PCR was performed to measure gene expression of proinflammatory cytokines of CMCs, tight junction (TJ) proteins of IECs, and muscle cell growth markers of QMCs and PMCs. In the second study, in vivo trials were carried out to study the effect of dietary ICOOH on disease parameters in broiler chickens infected with E. maxima. One hundred twenty male broiler chickens (0-day-old) were allocated into the following four treatment groups: 1) basal diet without infection (CON), 2) basal diet with E. maxima (NC), 3) ICOOH at 10.0 mg/kg feed with E. maxima (HI), and 4) ICOOH at 1.0 mg/kg feed with E. maxima (LO). Body weights (BWs) were measured on 0, 7, 14, 20, and 22 days. All groups except the CON chickens were orally infected with E. maxima on day 14. Jejunal samples were collected for lesion score and the transcriptomic analysis of cytokines and TJ proteins. In vitro, ICOOH increased the expression of TJ proteins in IECs and decreased IL-1β and IL-8 transcripts in the LPS-stimulated CMCs. In vivo, chickens on the HI diet showed reduced jejunal IL-1β, IFN-γ, and IL-10 expression and increased expression of genes activated by aryl hydrocarbon receptors and nutrient transporters in E. maxima-infected chickens. In conclusion, these results demonstrate the beneficial effects of dietary ICOOH on intestinal immune responses and barrier integrity in broiler chickens challenged with E. maxima. Furthermore, the present finding supports the notion to use microbial metabolites as novel feed additives to enhance resilience in animal agriculture.

show abstract

Section: Resultsmentioning

confidence: 99%

Gut Microbiota-Derived Indole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima

et al. 2022

View full text Add to dashboard Cite

show abstract

“…4‐AP ‐t‐ BOC is typically synthesized by the reaction of N‐ BOC‐4‐piperidone with aniline followed by the reduction of the imine (scheme shown in supporting information). 6,7 Di‐ t ‐butyl dicarbonate is widely used to introduce a t‐ BOC group into the molecule, and its reaction with 4‐AP could result in the protection of the piperidine and/or aniline nitrogen atoms. However, the nucleophilicity of the aniline nitrogen is greatly reduced through resonance with delocalization of the aniline nitrogen lone pair of electrons, and Mayr's Database of Reactivity suggests that aniline is approximately 10 000 times less nucleophilic than piperidine depending on the solvent 8 .…”

Section: Resultsmentioning

confidence: 99%

An unusual detection of tert‐butyl‐4‐anilinopiperidine‐1‐carboxylate in seizures of falsified ‘Xanax’ tablets and in items in a suspected heroin seizure submitted by Irish law enforcement

May

Downey

Power

et al. 2020

Drug Testing and Analysis

View full text Add to dashboard Cite

The identification of tert‐butyl‐4‐anilinopiperidine‐1‐carboxylate (4‐anilinopiperdine‐t‐BOC or 4‐AP‐t‐BOC) in many seized falsified ‘Xanax’ tablets has been reported after being encountered in forensic casework in late 2019 and early 2020 in Ireland. This substance was also detected in a pink powder submitted for analysis in March 2020. The pink powder was part of a larger seizure comprising brown powders which contained morphine or diamorphine (heroin) or a type of counterfeit heroin or heroin adulterant (known as ‘bash’). Novel benzodiazepines and other substances are being detected as ingredients in falsified benzodiazepine tablets more frequently on the illicit market. The detection of 4‐AP‐t‐BOC in benzodiazepine tablets is noteworthy and 4‐AP‐t‐BOC is added to the list of adulterants found in benzodiazepine tablets emerging in Europe. The presence of 4‐AP‐t‐BOC in both falsified ‘Xanax’ and powdered seizures is unusual, and analytical data are presented to assist with the identification of this compound in suspected illicit substances. The presence of 4‐AP‐t‐BOC in the tablets was confirmed using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry analyses, and spectral fragmentation pathways were suggested. To the authors' best knowledge, information about the biological activity of 4‐AP‐t‐BOC is not available. The removal of the t‐BOC protecting group yields 4‐anilinopiperidine which has been reported to be involved in the synthesis of fentanyl.

show abstract

“…Therefore, this work conveyed the disclosure of CAD as inhibitors of the new permeability pathways (NPP) induced by Plasmodium in erythrocytes to enable the translocation of carbohydrates and amino acids [46][47][48][49]. Following this pioneering discovery, other authors have proposed different CA-inspired compounds as potential therapeutic agents against malaria [26,28,29], as well as other parasitic diseases [50][51][52]. In view of this, reports have emerged over the past decade where conjugation to CA was proposed as a useful strategy for the rescuing of known antimalarials [53][54][55].…”

Section: Cinnamic Acid Conjugation In the Rescuing Of Classical Antimmentioning

confidence: 99%

“…Molecules 2020, 24, x FOR PEER REVIEW 3 of 15 malaria [26,28,29], as well as other parasitic diseases [50][51][52]. In view of this, reports have emerged over the past decade where conjugation to CA was proposed as a useful strategy for the rescuing of known antimalarials [53][54][55].…”

Section: Cinnamic Acid Conjugation In the Rescuing Of Classical Antimmentioning

confidence: 99%

“…These acids are frequently found in a conjugated form, constituting key building blocks of complex polyphenols, such as acylated derivatives of flavonoid glycosides [5], and they have a number of biological roles in plants, from protection against microbes long been explored for their potential therapeutic applications, most of which related to their antioxidant, antimicrobial, and antineoplastic properties [4,[7][8][9][10][11][12][13][14]. The potential of CA-based compounds as therapeutic agents for other conditions, including Alzheimer's Disease [15], other nervous system disorders [16,17], acute pain [18], inflammation [19], diabetes [20,21], viral infections [22], tuberculosis [23][24][25][26], and malaria [26][27][28][29], among others, has also been addressed. Depending on their therapeutic targets, different modes of action seem to be exerted by CA and their derivatives or analogues.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cinnamic Acid Conjugates in the Rescuing and Repurposing of Classical Antimalarial Drugs

et al. 2019

View full text Add to dashboard Cite

Cinnamic acids are compounds of natural origin that can be found in many different parts of a wide panoply of plants, where they play the most diverse biological roles, often in a conjugated form. For a long time, this has been driving Medicinal Chemists towards the investigation of the therapeutic potential of natural, semi-synthetic, or fully synthetic cinnamic acid conjugates. These efforts have been steadily disclosing promising drug leads, but a wide chemical space remains that deserves to be further explored. Amongst different reported approaches, the combination or conjugation of cinnamic acids with known drugs has been addressed in an attempt to produce either synergistic or multi-target action. In this connection, the present review will focus on efforts of the past decade regarding conjugation with cinnamic acids as a tool for the rescuing or the repurposing of classical antimalarial drugs, and also on future perspectives in this particular field of research.

show abstract

Synthesis and Antimalarial Activity of 1,4-Disubstituted Piperidine Derivatives

Cited by 21 publications

References 32 publications

Gut Microbiota-Derived Indole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima

Gut Microbiota-Derived Indole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima

An unusual detection of tert‐butyl‐4‐anilinopiperidine‐1‐carboxylate in seizures of falsified ‘Xanax’ tablets and in items in a suspected heroin seizure submitted by Irish law enforcement

Cinnamic Acid Conjugates in the Rescuing and Repurposing of Classical Antimalarial Drugs

Contact Info

Product

Resources

About