Structures and bioactivities of monomeric and dimeric carvotacetones from Sphaeranthus africanus

• Published in: Phytochemistry (Oxford) Vol. 218; p. 113938
• Main Authors: Tran, Huyen Thi, Pirker, Teresa, Pferschy-Wenzig, Eva-Maria, Kunert, Olaf, Huynh, Loi, Bauer, Rudolf
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.02.2024; Elsevier
• Subjects: Anti-proliferative; Apoptosis induction activity; Asteraceae; Asteraceae - chemistry; Biochemistry & Molecular Biology; Carvotacetones; Cell Line; Cyclohexanones; Humans; Inhibition of NO production; Life Sciences & Biomedicine; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Sciences; Science & Technology; Sphaeranthus africanus; Apoptosis induction activity; Carvotacetones; Anti-proliferative; Inhibition of NO production; Sphaeranthus africanus; Asteraceae; TARGET; CANCER-RELATED INFLAMMATION; PRIORITIES; INHIBITORS; NF-KAPPA-B; DERIVATIVES
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2023.113938

Four previously undescribed carvotacetones including one monomeric (1) and three dimeric (8, 9, 10) derivatives, together with six known compounds were isolated from the n-hexane extract of the aerial parts of Sphaeranthus africanus L. The structures of the previously undescribed compounds were elucidated as 3-angeloyloxy-5-isobutanoyloxy-7-hydroxycarvotacetone (1), 7,7′-oxybis{3-angeloyloxy-5-[(2R*,3R*)-2,3-dihydroxy-2-methylbutanoyloxy]carvotacetone} (8), (2″S*,3″R*)-7-{3-angeloyloxy-5-[(2R*,3R*)-2,3-dihydroxy-2-methylbuta-noyloxy]carvotaceton-7-yloxy}-3-angeloyloxy-5-(2,3-dihydroxy-2-methylbutanoyloxy)carvo-tacetone (9), and 7,7′-oxybis{3-angeloyloxy-5-[(2S*,3R*)-2,3-dihydroxy-2-methylbutanoyl-oxy]carvotacetone} (10). The three dimeric derivatives (8–10) showed potent anti-proliferative activity against human cancer cell lines (CCRF-CEM, MDA-MB-231, U-251, HCT-116) with IC50 values ranging from 0.2 to 2.0 μM. Caspases 3 and 7 were found to be activated by all compounds, indicating apoptosis induction activity. Monomers exhibited a specific inhibition of NO production in BV2 and RAW 264.7 cells with IC50 values ranging from 4.2 to 6.8 μM which were 2–3.5-fold lower than IC50 values causing cytotoxicity. In addition, the carvotacetones reduced NF-κB1 (p105) mRNA expression at concentrations of 10 and 2.5 μM. Altogether, the results indicate that carvotacetones may be interesting lead structures for the development of anti-cancer and anti-inflammatory drugs. [Display omitted] •Three new dimeric carvotacetones were isolated from Sphaeranthus africanus•The compounds showed potent anti-proliferative activity against cancer cell lines•Caspases 3 and 7 were found to be activated, indicating apoptosis induction activity•Carvotacetones exhibited inhibition of NO production in BV2 and RAW 264.7 cells•Isolated compounds reduced NF-κB1 (p105) mRNA expression