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Selective tumor cell growth inhibition by lignans and a seco -triterpenoid from Combretum mellifluum .

Patrick da Silva MirowskiMariáh OjedaLuiz Gustavo KolletTalita Vilalva FreireArnildo PottWalmir Silva GarcezRenata Trentin PerdomoFernanda Rodrigues Garcez
Published in: Natural product research (2022)
Two new tetrahydrofuran lignans 1-2 , along with 2,3- seco -lup-20(29)-en-2,3-dioic acid ( 3 ), (-)-larreatricin ( 4 ), and 15 additional compounds were isolated from Combretum mellifluum (Combretaceae). Their structures were determined by 1D- and 2D- NMR spectroscopic data and HRESIMS. Another 15 compounds were identified after HPLC-DAD-MS/MS analysis. Tested against HT-29 (colon) neoplastic cells, lignan 1 showed marked cytotoxicity (GI 50 = 3.9 µM) and high selectivity (SI > 227), compared with non-neoplastic NIH/3T3 cells, while 2 proved less cytotoxic, despite exhibiting SI > 75. Seco -triterpene 3 was strongly cytotoxic to 786-0 (kidney) and HT-29 cells (GI 50 = 0.5 and 2.9 µM, respectively), proving roughly 107 and 18 times more selective for these cell lines, respectively, than for NIH/3T3 cells. After 48 h of incubation, 1 - 3 exhibited potent cytostatic activity against HT-29 cells at all concentrations tested, while 3 had a cytocidal effect on 786-0 cells at 25 µg.mL -1 .
Keyphrases
  • induced apoptosis
  • ms ms
  • cell cycle arrest
  • endoplasmic reticulum stress
  • magnetic resonance
  • oxidative stress
  • cell death
  • mass spectrometry
  • signaling pathway
  • molecular docking
  • machine learning
  • pi k akt