Synthesis and Evaluation of C15 Triene Urushiol Derivatives as Potential Anticancer Agents and HDAC2 Inhibitor

Abstract

A series of C15 triene urushiol derivatives were synthesized and evaluated for their anti-HepG2 aggregation in vitro. The results indicated that all compounds had an effective anti-HepG2 vitality. Compound 1 was a potent inhibitor of HepG2 with IC50 of 7.886 μM and 150 μM against LO2. Moreover, compound 1 increased the apoptosis of HepG2. Compound 1’s thiol sulfur formed hydrogen bonding interactions with Gly154 and Tyr308, respectively, and made it bound more closely to HDAC2. In addition, it also formed hydrophobic interactions with the residues His33, Pro106, Val107, Gly154, Phe155, and His183, and was provided with a strong van der Waals force by the hydrophobic action.

Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study

“…As shown in Figure 1 and Figure 2 , all of the compounds ( 1 – 22 ) were evaluated for the inhibitory effects of the proliferation on HepG2 and LO2 cells using MTT assay. The quality structure–activity relationship (QSAR) of the above-mentioned urushiol derivatives proved that urushiol with the D–A structure in its alkyl chain, the pechmann structure; phenylboronic group [ 36 ]; and F-, Cl-, and Br-nitro substituents played an effective role in attenuating and increasing the efficiency; the urushiol triazole derivative also presented a same effect. However, unlike the ether bond, introducing alkyne was not beneficial for urushiol’s bioactivity.…”

“…The bioassays of the urushiol derivatives indicated that the C-2, C-7/C-8, and C-19/C-22 bonds are important for activating antitumor properties [ 36 ]. To further evaluate the inhibitory potencies of some of the synthesized compounds, we determined the half maximal inhibitory concentration (IC50) values of the compounds with high inhibition rate (>75%).…”

Design, Synthesis, and Biological Evaluation of New Urushiol Derivatives as Potent Class I Histone Deacetylase Inhibitors

“…[17] The development of inhibitors by small molecule modification of urushiol has been reported. For example, based on the phenol hydroxyl protection strategy, Zhiwen Qi et al [18][19] have synthesized HDAC2 1, 2, 3-triazole inhibitors via urushiol bisphenol hydroxyl modification, with IC 50 values reaching 2.83 μM for HepG2, substantially downregulating HDAC2 expression in tumor cells. However, the development of antitumor inhibitors by modifying the urushiol side chain and benzene ring has not been documented.…”

Synthesis of an urushiol derivative and its use for hydrolysis resistance in dentin adhesive

“…[20][21][22][23] Even though urushiol has antibacterial, anticancer, antioxidant and hydrophobic properties because of its catechol structure and alkyl chain, it is rarely used in dentistry. 16,[24][25][26] Urushiol nanolm was used in dentistry to create a clear overlay on appliances that improved their durability by increasing the mechanical strength and intrinsic hydrophobicity while reducing the cytotoxicity for antimicrobial applications. 27 Moreover, 0.01% urushiol was reported to exhibit strong antibacterial capacity against Streptococcus mutans and had little effect on the shear bond strength of self-etch adhesives.…”