In silico-guided synthesis of a new, highly soluble, and anti-melanoma flavone glucoside: Skullcapflavone II-6'-O-β-glucoside.

Autor: Chang TS; Department of Biological Sciences and Technology, National University of Tainan, Tainan, Taiwan., Ding HY; Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan., Wang TY; Biodiversity Research Center, Academia Sinica, Taipei, Taiwan., Wu JY; Department of Food Science, National Quemoy University, Kinmen, Taiwan., Tsai PW; Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan., Suratos KS; School of Chemical, Biological, Materials Engineering and Sciences, Mapúa University, Manila, Philippines.; School of Graduate Studies, Mapúa University, Manila, Philippines., Tayo LL; School of Chemical, Biological, Materials Engineering and Sciences, Mapúa University, Manila, Philippines.; Department of Biology, School of Health Sciences, Mapúa University, Makati, Philippines., Liu GC; Department of Biological Sciences and Technology, National University of Tainan, Tainan, Taiwan., Ting HJ; Department of Biological Sciences and Technology, National University of Tainan, Tainan, Taiwan.
Jazyk: angličtina
Zdroj: Biotechnology and applied biochemistry [Biotechnol Appl Biochem] 2024 Oct 24. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1002/bab.2685
Abstrakt: Guided by in silico analysis tools and biotransformation technology, new derivatives of natural compounds with heightened bioactivities can be explored and synthesized efficiently. In this study, in silico data mining and molecular docking analysis predicted that glucosides of skullcapflavone II (SKII) were new flavonoid compounds and had higher binding potential to oncogenic proteins than SKII. These benefits guided us to perform glycosylation of SKII by utilizing four glycoside hydrolases and five glycosyltransferases (GTs). Findings unveiled that exclusive glycosylation of SKII was achieved solely through the action of GTs, with Bacillus subtilis BsUGT489 exhibiting the highest catalytic glycosylation efficacy. Structure analysis determined the glycosylated product as a novel compound, skullcapflavone II-6'-O-β-glucoside (SKII-G). Significantly, the aqueous solubility of SKII-G exceeded its precursor, SKII, by 272-fold. Furthermore, SKII-G demonstrated noteworthy anti-melanoma activity against human A2058 cells, exhibiting an IC 50 value surpassing that of SKII by 1.4-fold. Intriguingly, no substantial cytotoxic effects were observed in a murine macrophage cell line, RAW 264.7. This promising anti-melanoma activity without adverse effects on macrophages suggests that SKII-G could be a potential candidate for further preclinical and clinical studies. The in silico tool-guided synthesis of a new, highly soluble, and potent anti-melanoma glucoside, SKII-G, provides a rational design to facilitate the future discovery of new and bioactive compounds.
(© 2024 International Union of Biochemistry and Molecular Biology, Inc.)
Databáze: MEDLINE
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