Discovery of Novel Mono-Carbonyl Curcumin Derivatives as Potential Anti-Hepatoma Agents

Abstract

Curcumin possesses a wide spectrum of liver cancer inhibition effects, yet it has chemical instability and poor metabolic properties as a drug candidate. To alleviate these problems, a series of new mono-carbonyl curcumin derivatives G1–G7 were designed, synthesized, and evaluated by in vitro and in vivo studies. Compound G2 was found to be the most potent derivative (IC50 = 15.39 μM) compared to curcumin (IC50 = 40.56 μM) by anti-proliferation assay. Subsequently, molecular docking, wound healing, transwell, JC-1 staining, and Western blotting experiments were performed, and it was found that compound G2 could suppress cell migration and induce cell apoptosis by inhibiting the phosphorylation of AKT and affecting the expression of apoptosis-related proteins. Moreover, the HepG2 cell xenograft model and H&E staining results confirmed that compound G2 was more effective than curcumin in inhibiting tumor growth. Hence, G2 is a promising leading compound with the potential to be developed as a chemotherapy agent for hepatocellular carcinoma.

Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies

“…In anti-proliferation experiments, G2 emerged as the most powerful derivative, relative to curcumin. Additional research employing molecular docking, wound healing, transwell, JC-1 staining, and Western blotting techniques revealed that G2 possesses the ability to impede apoptosis and cell migration by manipulating the expression of apoptosis-related proteins and impeding the phosphorylation of AKT [127]. Additionally, the effectiveness of G2 was verified in a xenograft model using HepG2 cells; H&E staining confirmed that it inhibited tumor development more effectively than curcumin [127].…”

“…This method is implemented by producing, modifying, or expressing three-dimensional structures of molecules and evaluating the physicochemical attributes associated with them. Chemical modeling enables medicinal chemists to predict the molecular and biological characteristics of therapeutic molecules, which is a significant asset in drug design [127,128]. Predicting molecular interactions is an essential component of molecular modeling.…”

“…Research conducted by Cao et al exemplifies this methodology. An assortment of innovative mono-carbonyl curcumin derivatives was formulated and manufactured, and their efficacy against hepatocellular carcinoma was assessed via in vitro and in vivo investigations [127]. In anti-proliferation experiments, G2 emerged as the most powerful derivative, relative to curcumin.…”