Selective tumor cell growth inhibition by lignans and a seco-triterpenoid from Combretum mellifluum. Issue 24 (17th December 2022)

• Record Type: Journal Article
• Authors: Mirowski, Patrick da Silva; Ojeda, Mariáh; Kollet, Luiz Gustavo; Freire, Talita Vilalva; Pott, Arnildo; Garcez, Walmir Silva; Perdomo, Renata Trentin; Garcez, Fernanda Rodrigues
• Is Part Of: Natural product research. Volume 36:Issue 24(2022)
• Page Start: 6224
• Page End: 6231
• Publication Date: 2022-12-17
• Subjects: Combretaceae -- Combretum mellifluum -- tetrahydrofuran lignans -- triterpenes -- antiproliferative activity -- cytocidal -- cytotoxicity; Natural products -- Periodicals; Natural products -- Research -- Periodicals; Biological Factors -- Periodicals; Biological Products -- Periodicals; 547
• DOI: 10.1080/14786419.2021.2024823
• Languages: English
• ISSNs: 1478-6419

Abstract

Abstract: 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 (GI50 = 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 (GI50 = 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 . GRAPHICAL ABSTRACT: UF0001