Synthesis and biological screening of a library of macamides as TNF-α inhibitors

Pérez, Víctor Tena; Ticona, Luis Apaza; Serban, Andreea M.; Gómez, Jesús Gómez; Sánchez, Ángel Rumbero

doi:10.1039/d0md00208a

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…The protocol developed by Tena Pérez et al [43] was used for this assay. RAW 264.7 cell (1 × 10 4 cells/well) were seeded on 96-well culture plates and incubated for 6 h. The cells were then pretreated with various concentrations of the samples (extract, fractions, and compounds) for 2 h before stimulation with 0.1 μg/mL of LPS with or without samples for 6 h. Supernatants were then collected and the protein expression levels of TNF-α were measured by using an ELISA kit according to the manufacturer's instructions (Diaclone Company).…”

Section: Tnf-α Inhibition Assaymentioning

confidence: 99%

Anti-inflammatory and Anti-arthritic Activities of Aqueous Extract and Flavonoids from Tripodanthus acutifolius Leaves in Mice Paw Oedema

Ticona

Serban

Ticona³

et al. 2021

Planta Medica International Open

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Tripodanthus acutifolius, commonly known as Jamillo, is an herbal remedy used in traditional Andean medicine to treat joint problems, such as sprains, dislocations, and rheumatic pain. This study aimed to evaluate the in vitro and in vivo anti-inflammatory and anti-arthritic activity of the aqueous extract and isolated compounds of T. acutifolius. A bioguided phytochemical analysis based on NMR/MS was performed to identify the compounds of the aqueous extract from T. acutifolius. The anti-inflammatory and anti-arthritic activity were evaluated by measuring inflammatory parameters (TNF-α, C-reactive protein, and fibrinogen) in murine models. The chemical structure determination led to the identification of four flavonoids: (E)-2’,4’-dihydroxy-6’-methoxy-chalcone (1), 6,2’,4’-trimethoxyflavone (2), 5,3’,4’-trihydroxy-6,7,8-trimethoxyflavone (3), and 5,4’-dihydroxy-6,7,8-trimethoxyflavone (4). All compounds inhibited the production of TNF-α in the RAW 264.7 cell line, with IC50 values of 0.78, 1.43, 5.73, and 9.71 μM, respectively. In addition, all flavonoids decreased the levels of TNF-α, C-reactive protein, and fibrinogen at a concentration of 5 mg/kg in murine models. Our research shows that these compounds isolated from T. acutifolius have anti-inflammatory and anti-arthritic properties, providing scientific evidence for the traditional use of this plant species.

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Section: Tnf-α Inhibition Assaymentioning

confidence: 99%

Anti-inflammatory and Anti-arthritic Activities of Aqueous Extract and Flavonoids from Tripodanthus acutifolius Leaves in Mice Paw Oedema

Ticona

Serban

Ticona³

et al. 2021

Planta Medica International Open

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Anti-inflammatory and Anti-arthritic Activities of Glycosylated Flavonoids from Syzygium jambos in Edematogenic Agent-Induced Paw Edema in Mice

Ticona

Pérez

Alejano

et al. 2021

Rev. Bras. Farmacogn.

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Two glycosylated flavonoids, the quercetin-3-O-β-d-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside and myricetin-3-O-β-d-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside, were isolated from the CH2Cl2/MeOH fraction of Syzygium jambos (L.) Alston, Myrtaceae. The structures of these compounds were elucidated by spectroscopic means. The cytotoxicity of the compounds was evaluated against the RAW 264.7 cell lines by the lactate dehydrogenase assay. All analyzed compounds were less cytotoxic than the positive control (actinomycin D, CC50 = 0.008 μM). The anti-inflammatory and anti-arthritic activities were evaluated by measuring inflammatory parameters in murine models. The two glycosylated flavonoids inhibited the production of tumor necrosis factor-α in RAW 264.7 cell line with IC50 of 1.68 and 1.11 μM, respectively. In addition, all flavonoids decreased the levels of tumor necrosis factor-α, C-reactive protein, and fibrinogen at a dose of 5 mg/kg in murine models. Graphical abstract

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Lepidium meyenii (Maca) Roots: UPLC-HRMS, Molecular Docking, and Molecular Dynamics

et al. 2022

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Lepidium meyenii or Maca is widely cultivated as a health care food supplement due to its nutritional and medicinal properties. Although there are a few in-depth studies evaluating Maca antihypertensive effects, the correlations between the chemical constituents and bioactivity of the plant have not been studied before. Thus, the roots were extracted using different solvents (aqueous, methanol, 50% methanol, and methylene chloride) and investigated for their antihypertensive and antioxidant activities through several in vitro assays. The methanolic extract exhibited the best renin and angiotensin converting enzyme (ACE) inhibitory activities with IC 50 values of 24.79 ± 1.3 ng/mL and 22.02 ± 1.1 ng/mL, respectively, along with the highest antioxidant activity. In total, 120 metabolites from different classes, e.g., alkylamides, alkaloids, glucosinolates, organic acids, and hydantoin derivatives, were identified in the methanolic extract using ultrahigh-performance liquid chromatography/high-resolution mass spectrometry (UPLC/HRMS). Molecular docking simulations were used to investigate the potential binding modes and the intermolecular interactions of the identified compounds with ACE and renin active sites. Glucotropaeolin, β-carboline alkaloids, succinic acid, and 2,4-dihydroxy-3,5-cyclopentyl dienoic acid showed the highest affinity to target the ACE with high docking scores ( S ranging from −35.32 to −22.51 kcal mol –1 ) compared to lisinopril ( S = −36.64 kcal mol –1 ). Interestingly, macamides displayed the greatest binding affinity to the active site of renin with docking scores ( S ranging from −22.47 to −28.25 kcal mol –1 ). Further, β-carbolines achieved docking scores comparable to that of the native ligand ( S ranging from −13.50 to −20.06 kcal mol –1 ). Molecular dynamics simulations and MMPBSA were also carried out and confirmed the docking results. Additionally, the computational ADMET study predicted that the compounds attaining promising docking results had proper pharmacokinetics, drug-likeness characteristics, and safe toxicological profiles. Ultimately, our findings revealed that Maca roots could be considered a promising candidate as an antihypertensive drug.

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Synthesis and biological screening of a library of macamides as TNF-α inhibitors

Abstract: Thirty-five macamide analogues were synthesised by modifying the initial molecular structure.

Cited by 3 publications

References 31 publications

Anti-inflammatory and Anti-arthritic Activities of Aqueous Extract and Flavonoids from Tripodanthus acutifolius Leaves in Mice Paw Oedema

Anti-inflammatory and Anti-arthritic Activities of Aqueous Extract and Flavonoids from Tripodanthus acutifolius Leaves in Mice Paw Oedema

Anti-inflammatory and Anti-arthritic Activities of Glycosylated Flavonoids from Syzygium jambos in Edematogenic Agent-Induced Paw Edema in Mice

Lepidium meyenii (Maca) Roots: UPLC-HRMS, Molecular Docking, and Molecular Dynamics

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