The influence of a single and double biotinylation of xanthohumol on its anticancer activity

Abstract

Two biotinylated derivatives of the main hop chalcone xanthohumol (1) were prepared by a one-step synthesis via esterification using biotin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC×HCl) and 4-dimethylaminopyridine (DMAP) as coupling reagents. The products were characterized spectroscopically and their antiproliferative activity toward MCF-7, MCF-10A, HepG2, MDA-MB-231, 4T1 and Balb/3T3 cell lines was investigated using the SRB assay. For all three tested compounds the best activity was noted in the case of human (MCF-7) and mice (4T1) breast cancer cell lines (IC50 values < 9 μM). Both biotinylated derivatives showed slightly higher anticancer activity than xanthohumol (1) towards all types of tested breast cancer cells. Double biotinylated xanthohumol (3) proved to be the most active in inhibiting cell growth, with IC50 values equal to 5.35 ± 1.5 μM for 4T1 and 8.03 ± 0.53 µM for MCF-7 cell lines. Compound 3 was also more active than 1 and 2 against liver cancer cells HepG2 (IC50 = 17.37 ± 5.1 μM), while the IC50 values for 1 and 2 were equal to 21.5 ± 2.7 and 22.1 ± 3.9 µM, respectively. 4‑O‑biotinylxanthohumol (2) was the second most active growth inhibitor, particularly with respect to MCF-7 (IC50 = 6.19 ± 1.7 μM) and 4T1 (IC50 = 6.64 ± 0.4 μM) cell lines. Our preliminary study on biotinylated xanthohumol (1) have shown that this type of functionalization is an effective method for the production of active biomolecules and study on this area should be continued thereby extending their applications.

A Review on Sources and Pharmacological Aspects of Sakuranetin

“…In the human organism, they exert numerous beneficial health effects. The best known are anticancer, antioxidant, antiinflammatory, antiviral, antidiabetic, antimutagenic and antimicrobial ones [1][2][3][4][5][6]. Some of these compounds were also characterised as exerting beneficial physiological effects.…”

Xanthohumol from Hop: Hope for cancer prevention and treatment

“…Another study reported the synthesis of two biotinylated derivatives of XN prepared through esterification and its anti‐cancer activity was analyzed in different cancer cell lines. The highest efficacy was observed in MCF‐7 and 4T1 breast cancer cells and the analogue compound with double biotinylated XN (Figure 1j) showed highest activity in MCF‐7 and 4T1 breast cancer cells and HepG2 liver cancer cells, followed by the efficacy of other analogue, 4‐ O ‐biotinyl XN (Figure 1k) and original compound XN 62 . Thus, XN and its analogues are effective compounds against cancer and the modification of the structure of XN paves the way to improve the efficacy of the compound in the prevention and treatment of cancer.…”

“…Source, structure, and analogues of Xanthohumol. (a) Humulus lupulus plant (Photograph by: Craig Chandler, University Communication) ( https://cropwatch.unl.edu), (b) Xanthohumol, (c) Analogue 13n 58 ; (d) Compound 11 59 ; (e) Compound 12 59 ; (f) Naringenin 60 ; (g) Chalconaringenin 60 ; (h) 4‐hydroxy‐4′‐methoxychalcone 60 ; (i) Compound number 13 (with para‐methoxy and fluorine groups on B ring) 61 ; (j) Double biotinylated XN 62 ; (k) 4‐ O ‐biotinyl XN 62 …”

The Pro-Health Benefits of Morusin Administration—An Update Review

“…Natural compounds, including polyphenols with an isoprenyl group, due to their high potential for medical use, nowadays play an important role in the development of new molecularly targeted drugs, dietary supplements or antimicrobial agents [ 27 ]. Along with the development of biological therapeutic methods, these substances started to be used as standards or as substrates to obtain new derivatives [ 28 ].…”