» Articles » PMID: 39521925

Structurally Diverse Bufadienolides from the Skins of Bufo Bufo Gargarizans and Their Cytotoxicity

Overview
Journal Sci Rep
Specialty Science
Date 2024 Nov 9
PMID 39521925
Authors
Affiliations
Soon will be listed here.
Abstract

Natural products, with their extensive chemical diversity, distinctive biological activities, and vast reservoirs, provide a robust foundation for advancing cancer therapeutics. A comprehensive phytochemical investigation of the skins from Bufo bufo gargarizans afforded two new bufadienolide derivatives identified as bufalactamides A and B (1-2), along with six known compounds: argentinogenin (3), desacetylcinobufagin (4), desacetylcinobufaginol (5), cinobufaginol (6), bufalin (7) and gamabufalin (8). The structural elucidation of these compounds was meticulously carried out by analyses of spectroscopic data (1D and 2D NMR, HR-ESIMS), and comparison with the literature data. Plausible biosynthetic pathways for the new compounds were also discussed. Moreover, the cytotoxicity of the compounds was investigated using various cancer cell lines, including lung cancer (A549), colon cancer (HCT-116), liver cancer (SK-Hep-1), and ovarian cancer (SKOV3). Our research findings indicated that compounds 3, and 6-8 exhibit potent cytotoxic activity (IC < 2.5 µM). In contrast, compounds 4 and 5 display moderate cytotoxic activity (IC < 50 µM) while compounds 1 and 2 show no cytotoxic activity (IC > 100 µM). From this data, we conducted a comprehensive analysis of the structure-activity relationships among these compounds.

References
1.
Zhao J, Xu L, Li L, Ren G, Shao Y, Liu Q . Traditional Chinese medicine bufalin inhibits infectious hematopoietic necrosis virus infection and . Microbiol Spectr. 2024; 12(3):e0501622. PMC: 10913368. DOI: 10.1128/spectrum.05016-22. View

2.
Ruan L, Song Z, Jiang R . 3α-Hydroxybufadienolides in Bufo gallbladders: structural insights and biotransformation. Nat Prod Bioprospect. 2024; 14(1):19. PMC: 10912398. DOI: 10.1007/s13659-024-00442-2. View

3.
Li B, Tian H, Zhang D, Lei Y, Wang L, Jiang R . Bufadienolides with cytotoxic activity from the skins of Bufo bufo gargarizans. Fitoterapia. 2015; 105:7-15. DOI: 10.1016/j.fitote.2015.05.013. View

4.
Jiang N, Li S, Meng L, Zhang Y, Yu C, Xiao Y . Gamabufotalin inhibits colitis-associated colorectal cancer by suppressing transcription factor STAT3. Eur J Pharmacol. 2024; 966:176372. DOI: 10.1016/j.ejphar.2024.176372. View

5.
Xiang C, Fu Y, Hao T, Wei L, Liu Y, Fan Z . Podophyllotoxin-loaded PEGylated E-selectin peptide conjugate targeted cancer site to enhance tumor inhibition and reduce side effect. Eur J Med Chem. 2023; 260:115780. DOI: 10.1016/j.ejmech.2023.115780. View