Bioactive Isocedrenes from Perezia multiflora.
Sandra Bourgeade-DelmasChristiane André-BarrèsJeanne LucasManon TrinelDenis Castillo ParejaValérie JullianPublished in: Planta medica (2020)
Four isocedrenes (1: - 4: ), including one new compound (2: ), were isolated from an ethanolic extract of the aerial parts of Perezia multiflora by bioactivity-guided fractionation. For compounds 1: and 3: , a revised stereochemical assignment is proposed based on molecular modeling studies using DFT-NMR calculations. Antiparasitic activity of the four compounds was evaluated using an in vitro culture of Plasmodium falciparum and axenic amastigotes of Leishmania infantum. IC50 values ranged from 0.81 to 16.1 µM (P. falciparum) and 0.16 to 2.03 µM (L. infantum). Toxicity was evaluated against J774A.1 mouse macrophages or human macrophages generated from THP-1 monocytic cells (IC50 values ranging from 0.16 to 2.64 µM). Compound 4: exhibited weak selectivity against P. falciparum with a selectivity index (SI = CC50/IC50) of 3. No selectivity was observed for compounds 1: - 3: against both parasites.
Keyphrases
- plasmodium falciparum
- density functional theory
- induced apoptosis
- oxidative stress
- endothelial cells
- cell cycle arrest
- structural basis
- high resolution
- molecular dynamics
- molecular dynamics simulations
- cell death
- endoplasmic reticulum stress
- induced pluripotent stem cells
- mass spectrometry
- cell proliferation
- pi k akt
- signaling pathway