Synthesis of Curcumin Glycosides with Enhanced Anticancer Properties Using One-Pot Multienzyme Glycosylation Technique

Abstract

Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, antiinflammatory, antibacterial, and anticancerous properties. However, its use has been limited due to its low-aqueous solubility and poor bioavailability, rapid clearance, and low cellular uptake. In order to assess the effect of glycosylation on the pharmacological properties of curcumin, one-pot multienzyme (OPME) chemoenzymatic glycosylation reactions with UDPα-D-glucose or UDP-α-D-2-deoxyglucose as donor substrate were employed. The result indicated significant conversion of curcumin to its glycosylated derivatives: curcumin 4'-O-βglucoside, curcumin 4',4''-di-O-β-glucoside, curcumin 4'-O-β-2-deoxyglucoside, and curcumin 4',4''-di-O-β-2-deoxyglucoside. The products were characterized by ultra-fast performance liquid chromatography, high-resolution quadruple-time-of-flight electrospray ionization-mass spectrometry, and NMR analyses. All the products showed improved water solubility and comparable antibacterial activities. Additionally, the curcumin 4'-O-β-glucoside and curcumin 4'-O-β-2-deoxyglucoside showed enhanced anticancer activities compared with the parent aglycone and diglycoside derivatives. This result indicates that glycosylation can be an effective approach for enhancing the pharmaceutical properties of different natural products, such as curcumin.

<p>Evaluation of Intestinal Absorption Mechanism and Pharmacokinetics of Curcumin-Loaded Galactosylated Albumin Nanoparticles</p>

“…While the Cur group showed the weak green florescence because of the curcumin inside the cells. The poor aqueous solubility of curcumin influenced the internalization efficiency into the cells, which further reduced its therapeutic efficacy 25,26. After 4 hrs of incubation, the green fluorescence intensity in Gal-BSA-Cur NPs group was stronger than that in the Cur group, which indicated that Gal-BSA NPs could enhance the ability of internalization of curcumin into the cells and release more curcumin in the cytoplasm as well as in the nucleus.…”

Synthesis and Bioactivities of Novel 1,3,4-Thiadiazole Derivatives of Glucosides

“…Glycosides are secondary metabolites that widely exist in all organs of plants, such as flowers, fruits, leaves, skins, and roots, etc ( Gruner et al, 2002 ), and previous studies found that glycosides had a wide range of pharmacological activities, such as antiviral ( Chen W. et al, 2019 ; Khodair et al, 2019 ), antibacterial ( Mohammed et al, 2019 ), anticancer ( Gurung et al, 2018 ; Rahim et al, 2020 ), antioxidant ( Jiang et al, 2018 ; Hawas et al, 2019 ), and anti-HIV ( He et al, 2019 ) activities. Meanwhile, studies also found that glycoside derivatives showed exceeding inhibitory activities against plant pathogens.…”

“…In addition, it was also found that glycosylation is one of the effective ways to improve the functional activity of active lead compounds and develop new drugs. ( Gurung et al, 2018 ; Wu et al, 2014 ).…”

The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells

“…Notwithstanding its anti-cancer properties, clinical trial and pharmacokinetic data on curcumin displayed poor absorption and bio distribution, low bioavailability [ 17 , 18 , 19 ], inadequate biological stability [ 20 ], poor aqueous solubility [ 20 , 21 ], rapid metabolism [ 22 ], and rapid systemic elimination [ 19 , 23 ]. Curcumin which is hydrophobic [ 20 ] undergone biotransformation into curcumin glucuronides in the intestine and liver [ 24 , 25 ], which it is rapidly metabolized [ 22 ] and eliminate via feces [ 20 , 23 , 26 ].…”